<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2024 Workiva-->
<!--r:a6cf088c-e54c-4ffd-b839-41926fb0966e,g:4ff84466-72ad-4f3e-be53-c78a1eb796c9-->
<xs:schema xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:mdgl="http://www.madrigalpharma.com/20240930" xmlns:xbrli="http://www.xbrl.org/2003/instance" xmlns:dtr-types1="http://www.xbrl.org/dtr/type/2020-01-21" xmlns:dtr-types="http://www.xbrl.org/dtr/type/2022-03-31" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" attributeFormDefault="unqualified" elementFormDefault="qualified" targetNamespace="http://www.madrigalpharma.com/20240930">
  <xs:import namespace="http://fasb.org/srt/2023" schemaLocation="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd"/>
  <xs:import namespace="http://fasb.org/us-gaap/2023" schemaLocation="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd"/>
  <xs:import namespace="http://www.xbrl.org/2003/instance" schemaLocation="http://www.xbrl.org/2003/xbrl-instance-2003-12-31.xsd"/>
  <xs:import namespace="http://www.xbrl.org/2003/linkbase" schemaLocation="http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd"/>
  <xs:import namespace="http://www.xbrl.org/dtr/type/2020-01-21" schemaLocation="https://www.xbrl.org/dtr/type/2020-01-21/types.xsd"/>
  <xs:import namespace="http://www.xbrl.org/dtr/type/2022-03-31" schemaLocation="https://www.xbrl.org/dtr/type/2022-03-31/types.xsd"/>
  <xs:import namespace="http://xbrl.org/2005/xbrldt" schemaLocation="http://www.xbrl.org/2005/xbrldt-2005.xsd"/>
  <xs:import namespace="http://xbrl.sec.gov/dei/2023" schemaLocation="https://xbrl.sec.gov/dei/2023/dei-2023.xsd"/>
  <xs:import namespace="http://xbrl.sec.gov/ecd/2023" schemaLocation="https://xbrl.sec.gov/ecd/2023/ecd-2023.xsd"/>
  <xs:annotation>
    <xs:appinfo>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="mdgl-20240930_pre.xml" xlink:role="http://www.xbrl.org/2003/role/presentationLinkbaseRef" xlink:type="simple"/>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="mdgl-20240930_def.xml" xlink:role="http://www.xbrl.org/2003/role/definitionLinkbaseRef" xlink:type="simple"/>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="mdgl-20240930_lab.xml" xlink:role="http://www.xbrl.org/2003/role/labelLinkbaseRef" xlink:type="simple"/>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="mdgl-20240930_cal.xml" xlink:role="http://www.xbrl.org/2003/role/calculationLinkbaseRef" xlink:type="simple"/>
      <link:roleType id="CoverPage" roleURI="http://www.madrigalpharma.com/role/CoverPage">
        <link:definition>0000001 - Document - Cover Page</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CONDENSEDCONSOLIDATEDBALANCESHEETS" roleURI="http://www.madrigalpharma.com/role/CONDENSEDCONSOLIDATEDBALANCESHEETS">
        <link:definition>0000002 - Statement - CONDENSED CONSOLIDATED BALANCE SHEETS</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CONDENSEDCONSOLIDATEDBALANCESHEETSParenthetical" roleURI="http://www.madrigalpharma.com/role/CONDENSEDCONSOLIDATEDBALANCESHEETSParenthetical">
        <link:definition>0000003 - Statement - CONDENSED CONSOLIDATED BALANCE SHEETS (Parenthetical)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CONDENSEDCONSOLIDATEDSTATEMENTSOFOPERATIONS" roleURI="http://www.madrigalpharma.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFOPERATIONS">
        <link:definition>0000004 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CONDENSEDCONSOLIDATEDSTATEMENTSOFCOMPREHENSIVELOSS" roleURI="http://www.madrigalpharma.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFCOMPREHENSIVELOSS">
        <link:definition>0000005 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CONDENSEDCONSOLIDATEDSTATEMENTSOFSTOCKHOLDERSEQUITY" roleURI="http://www.madrigalpharma.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFSTOCKHOLDERSEQUITY">
        <link:definition>0000006 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS&#8217; EQUITY</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CONDENSEDCONSOLIDATEDSTATEMENTSOFCASHFLOWS" roleURI="http://www.madrigalpharma.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFCASHFLOWS">
        <link:definition>0000007 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="OrganizationBusinessandBasisofPresentation" roleURI="http://www.madrigalpharma.com/role/OrganizationBusinessandBasisofPresentation">
        <link:definition>0000008 - Disclosure - Organization, Business and Basis of Presentation</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPolicies" roleURI="http://www.madrigalpharma.com/role/SummaryofSignificantAccountingPolicies">
        <link:definition>0000009 - Disclosure - Summary of Significant Accounting Policies</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="LiquidityandUncertainties" roleURI="http://www.madrigalpharma.com/role/LiquidityandUncertainties">
        <link:definition>0000010 - Disclosure - Liquidity and Uncertainties</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CashCashEquivalentsandMarketableSecurities" roleURI="http://www.madrigalpharma.com/role/CashCashEquivalentsandMarketableSecurities">
        <link:definition>0000011 - Disclosure - Cash, Cash Equivalents and Marketable Securities</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="Inventory" roleURI="http://www.madrigalpharma.com/role/Inventory">
        <link:definition>0000012 - Disclosure - Inventory</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AccruedLiabilities" roleURI="http://www.madrigalpharma.com/role/AccruedLiabilities">
        <link:definition>0000013 - Disclosure - Accrued Liabilities</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="LongTermDebt" roleURI="http://www.madrigalpharma.com/role/LongTermDebt">
        <link:definition>0000014 - Disclosure - Long Term Debt</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockholdersEquity" roleURI="http://www.madrigalpharma.com/role/StockholdersEquity">
        <link:definition>0000015 - Disclosure - Stockholders' Equity</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockbasedCompensation" roleURI="http://www.madrigalpharma.com/role/StockbasedCompensation">
        <link:definition>0000016 - Disclosure - Stock-based Compensation</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommitmentsandContingencies" roleURI="http://www.madrigalpharma.com/role/CommitmentsandContingencies">
        <link:definition>0000017 - Disclosure - Commitments and Contingencies</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SubsequentEvents" roleURI="http://www.madrigalpharma.com/role/SubsequentEvents">
        <link:definition>0000018 - Disclosure - Subsequent Events</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPoliciesPolicies" roleURI="http://www.madrigalpharma.com/role/SummaryofSignificantAccountingPoliciesPolicies">
        <link:definition>9954471 - Disclosure - Summary of Significant Accounting Policies (Policies)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPoliciesTables" roleURI="http://www.madrigalpharma.com/role/SummaryofSignificantAccountingPoliciesTables">
        <link:definition>9954472 - Disclosure - Summary of Significant Accounting Policies (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CashCashEquivalentsandMarketableSecuritiesTables" roleURI="http://www.madrigalpharma.com/role/CashCashEquivalentsandMarketableSecuritiesTables">
        <link:definition>9954473 - Disclosure - Cash, Cash Equivalents and Marketable Securities (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="InventoryTables" roleURI="http://www.madrigalpharma.com/role/InventoryTables">
        <link:definition>9954474 - Disclosure - Inventory (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AccruedLiabilitiesTables" roleURI="http://www.madrigalpharma.com/role/AccruedLiabilitiesTables">
        <link:definition>9954475 - Disclosure - Accrued Liabilities (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="LongTermDebtTables" roleURI="http://www.madrigalpharma.com/role/LongTermDebtTables">
        <link:definition>9954476 - Disclosure - Long Term Debt (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockbasedCompensationTables" roleURI="http://www.madrigalpharma.com/role/StockbasedCompensationTables">
        <link:definition>9954477 - Disclosure - Stock-based Compensation (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPoliciesConcentrationsofCreditRiskandSignificantCustomersDetails" roleURI="http://www.madrigalpharma.com/role/SummaryofSignificantAccountingPoliciesConcentrationsofCreditRiskandSignificantCustomersDetails">
        <link:definition>9954478 - Disclosure - Summary of Significant Accounting Policies - Concentrations of Credit Risk and Significant Customers (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPoliciesMarketableSecuritiesDetails" roleURI="http://www.madrigalpharma.com/role/SummaryofSignificantAccountingPoliciesMarketableSecuritiesDetails">
        <link:definition>9954479 - Disclosure - Summary of Significant Accounting Policies - Marketable Securities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPoliciesIncomeTaxesDetails" roleURI="http://www.madrigalpharma.com/role/SummaryofSignificantAccountingPoliciesIncomeTaxesDetails">
        <link:definition>9954480 - Disclosure - Summary of Significant Accounting Policies - Income Taxes (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPoliciesBasicandDilutedLossPerCommonShareDetails" roleURI="http://www.madrigalpharma.com/role/SummaryofSignificantAccountingPoliciesBasicandDilutedLossPerCommonShareDetails">
        <link:definition>9954481 - Disclosure - Summary of Significant Accounting Policies - Basic and Diluted Loss Per Common Share (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="LiquidityandUncertaintiesDetails" roleURI="http://www.madrigalpharma.com/role/LiquidityandUncertaintiesDetails">
        <link:definition>9954482 - Disclosure - Liquidity and Uncertainties (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CashCashEquivalentsandMarketableSecuritiesNarrativeDetails" roleURI="http://www.madrigalpharma.com/role/CashCashEquivalentsandMarketableSecuritiesNarrativeDetails">
        <link:definition>9954483 - Disclosure - Cash, Cash Equivalents and Marketable Securities - Narrative (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CashCashEquivalentsandMarketableSecuritiesCashCashEquivalentsandAvailableforSaleMarketableSecuritiesDetails" roleURI="http://www.madrigalpharma.com/role/CashCashEquivalentsandMarketableSecuritiesCashCashEquivalentsandAvailableforSaleMarketableSecuritiesDetails">
        <link:definition>9954484 - Disclosure - Cash, Cash Equivalents and Marketable Securities - Cash, Cash Equivalents and Available-for-Sale Marketable Securities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CashCashEquivalentsandMarketableSecuritiesCashCashEquivalentsandAvailableforSaleMarketableSecuritiesDetails_1" roleURI="http://www.madrigalpharma.com/role/CashCashEquivalentsandMarketableSecuritiesCashCashEquivalentsandAvailableforSaleMarketableSecuritiesDetails_1">
        <link:definition>9954484 - Disclosure - Cash, Cash Equivalents and Marketable Securities - Cash, Cash Equivalents and Available-for-Sale Marketable Securities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="InventoryDetails" roleURI="http://www.madrigalpharma.com/role/InventoryDetails">
        <link:definition>9954485 - Disclosure - Inventory (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AccruedLiabilitiesDetails" roleURI="http://www.madrigalpharma.com/role/AccruedLiabilitiesDetails">
        <link:definition>9954486 - Disclosure - Accrued Liabilities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="LongTermDebtNarrativeDetails" roleURI="http://www.madrigalpharma.com/role/LongTermDebtNarrativeDetails">
        <link:definition>9954487 - Disclosure - Long Term Debt - Narrative (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="LongTermDebtMaturitiesofLongTermDebtDetails" roleURI="http://www.madrigalpharma.com/role/LongTermDebtMaturitiesofLongTermDebtDetails">
        <link:definition>9954488 - Disclosure - Long Term Debt - Maturities of Long-Term Debt (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockholdersEquityCommonStockDetails" roleURI="http://www.madrigalpharma.com/role/StockholdersEquityCommonStockDetails">
        <link:definition>9954489 - Disclosure - Stockholders' Equity- Common Stock (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockholdersEquityPreferredStockDetails" roleURI="http://www.madrigalpharma.com/role/StockholdersEquityPreferredStockDetails">
        <link:definition>9954490 - Disclosure - Stockholders' Equity - Preferred Stock (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockholdersEquityPublicOfferingDetails" roleURI="http://www.madrigalpharma.com/role/StockholdersEquityPublicOfferingDetails">
        <link:definition>9954491 - Disclosure - Stockholders' Equity - Public Offering (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockholdersEquityAtTheMarketIssuancesDetails" roleURI="http://www.madrigalpharma.com/role/StockholdersEquityAtTheMarketIssuancesDetails">
        <link:definition>9954492 - Disclosure - Stockholders' Equity - At The Market Issuances (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockbasedCompensationNarrativeDetails" roleURI="http://www.madrigalpharma.com/role/StockbasedCompensationNarrativeDetails">
        <link:definition>9954493 - Disclosure - Stock-based Compensation - Narrative (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockbasedCompensationStockOptionDetails" roleURI="http://www.madrigalpharma.com/role/StockbasedCompensationStockOptionDetails">
        <link:definition>9954494 - Disclosure - Stock-based Compensation - Stock Option (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockbasedCompensationRestrictedStockUnitsDetails" roleURI="http://www.madrigalpharma.com/role/StockbasedCompensationRestrictedStockUnitsDetails">
        <link:definition>9954495 - Disclosure - Stock-based Compensation - Restricted Stock Units (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockbasedCompensationPerformanceBasedRestrictedStockUnitsDetails" roleURI="http://www.madrigalpharma.com/role/StockbasedCompensationPerformanceBasedRestrictedStockUnitsDetails">
        <link:definition>9954496 - Disclosure - Stock-based Compensation - Performance-Based Restricted Stock Units (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockbasedCompensationStockBasedCompensationExpenseDetails" roleURI="http://www.madrigalpharma.com/role/StockbasedCompensationStockBasedCompensationExpenseDetails">
        <link:definition>9954497 - Disclosure - Stock-based Compensation - Stock-Based Compensation Expense (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommitmentsandContingenciesDetails" roleURI="http://www.madrigalpharma.com/role/CommitmentsandContingenciesDetails">
        <link:definition>9954498 - Disclosure - Commitments and Contingencies (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
    </xs:appinfo>
  </xs:annotation>
  <xs:element id="mdgl_OperatingLeaseRightOfUseAssetPeriodicReductionIncrease" abstract="false" name="OperatingLeaseRightOfUseAssetPeriodicReductionIncrease" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="mdgl_IncreaseDecreaseInAccruedInterestNetOfInterestReceived" abstract="false" name="IncreaseDecreaseInAccruedInterestNetOfInterestReceived" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="mdgl_LiquidityAndUncertaintiesDisclosureAbstract" abstract="true" name="LiquidityAndUncertaintiesDisclosureAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="mdgl_PatentsPolicyTextBlock" abstract="false" name="PatentsPolicyTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:textBlockItemType"/>
  <xs:element id="mdgl_CustomerAMember" abstract="true" name="CustomerAMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="mdgl_CustomersBMember" abstract="true" name="CustomersBMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="mdgl_CustomersCMember" abstract="true" name="CustomersCMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="mdgl_CustomersDMember" abstract="true" name="CustomersDMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="mdgl_DeferredTaxAssetsPercentageOfValuationAllowance" abstract="false" name="DeferredTaxAssetsPercentageOfValuationAllowance" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:percentItemType"/>
  <xs:element id="mdgl_CorporateDebtSecuritiesDueWithinOneToTwoYearsOfDateOfPurchaseMember" abstract="true" name="CorporateDebtSecuritiesDueWithinOneToTwoYearsOfDateOfPurchaseMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="mdgl_USTreasuryAndGovernmentDueWithinOneYearMember" abstract="true" name="USTreasuryAndGovernmentDueWithinOneYearMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="mdgl_USTreasuryAndGovernmentDueWithinOneToTwoYearsMember" abstract="true" name="USTreasuryAndGovernmentDueWithinOneToTwoYearsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="mdgl_CashCashEquivalentsAndShortTermInvestmentsAtCost" abstract="false" name="CashCashEquivalentsAndShortTermInvestmentsAtCost" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="mdgl_AccruedContractResearchCostsCurrent" abstract="false" name="AccruedContractResearchCostsCurrent" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="mdgl_AccruedOtherClinicalStudyRelatedCostsCurrent" abstract="false" name="AccruedOtherClinicalStudyRelatedCostsCurrent" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="mdgl_AccruedManufacturingAndDrugSupplyCurrent" abstract="false" name="AccruedManufacturingAndDrugSupplyCurrent" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="mdgl_AccruedLiabilitiesGross" abstract="false" name="AccruedLiabilitiesGross" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="mdgl_LoanFacilityMember" abstract="true" name="LoanFacilityMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="mdgl_LoanFacilityTrancheOneMember" abstract="true" name="LoanFacilityTrancheOneMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="mdgl_LoanFacilityTranchesTwoAndThreeMember" abstract="true" name="LoanFacilityTranchesTwoAndThreeMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="mdgl_LoanFacilityTrancheTwoMember" abstract="true" name="LoanFacilityTrancheTwoMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="mdgl_LoanFacilityTrancheThreeMember" abstract="true" name="LoanFacilityTrancheThreeMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="mdgl_LoanFacilityTrancheFourMember" abstract="true" name="LoanFacilityTrancheFourMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="mdgl_VariableRateComponentAxis" abstract="true" name="VariableRateComponentAxis" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrldt:dimensionItem" type="xbrli:stringItemType"/>
  <xs:element id="mdgl_VariableRateComponentDomain" abstract="true" name="VariableRateComponentDomain" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="mdgl_VariableRateComponentOneMember" abstract="true" name="VariableRateComponentOneMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="mdgl_VariableRateComponentTwoMember" abstract="true" name="VariableRateComponentTwoMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="mdgl_HerculesWarrantsMember" abstract="true" name="HerculesWarrantsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="mdgl_LineOfCreditFacilityNumberOfWithdrawalsUponMilestoneAchievements" abstract="false" name="LineOfCreditFacilityNumberOfWithdrawalsUponMilestoneAchievements" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="mdgl_LongTermDebtFloorInterestRatePercentage" abstract="false" name="LongTermDebtFloorInterestRatePercentage" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="dtr-types1:percentItemType"/>
  <xs:element id="mdgl_DebtInstrumentAccruedInterestPaymentsTerm" abstract="false" name="DebtInstrumentAccruedInterestPaymentsTerm" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:durationItemType"/>
  <xs:element id="mdgl_LineOfCreditFacilityIncreaseInMaximumBorrowingCapacity" abstract="false" name="LineOfCreditFacilityIncreaseInMaximumBorrowingCapacity" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="mdgl_LineOfCreditFacilityDecreaseInMaximumBorrowingCapacity" abstract="false" name="LineOfCreditFacilityDecreaseInMaximumBorrowingCapacity" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="mdgl_DebtInstrumentCovenantLiquidityMinimum" abstract="false" name="DebtInstrumentCovenantLiquidityMinimum" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="mdgl_LongTermDebtMaturityAfterYearTwo" abstract="false" name="LongTermDebtMaturityAfterYearTwo" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="mdgl_CommonStockVotingRightsNumber" abstract="false" name="CommonStockVotingRightsNumber" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="mdgl_ConvertibleSeriesAAndBPreferredStockMember" abstract="true" name="ConvertibleSeriesAAndBPreferredStockMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="mdgl_PreferredStockNumberOfVotingRights" abstract="false" name="PreferredStockNumberOfVotingRights" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="mdgl_PublicOffering2024Member" abstract="true" name="PublicOffering2024Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="mdgl_PublicOffering2023Member" abstract="true" name="PublicOffering2023Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="mdgl_PreFundedWarrantsMember" abstract="true" name="PreFundedWarrantsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="mdgl_ClassOfWarrantOrRightStockPriceDiscountPerCommonShare" abstract="false" name="ClassOfWarrantOrRightStockPriceDiscountPerCommonShare" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="dtr-types:perShareItemType"/>
  <xs:element id="mdgl_SaleOfStockPurchasingPeriod" abstract="false" name="SaleOfStockPurchasingPeriod" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:durationItemType"/>
  <xs:element id="mdgl_SaleOfStockConsiderationReceivedOnTransactionGross" abstract="false" name="SaleOfStockConsiderationReceivedOnTransactionGross" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="mdgl_ClassOfWarrantOrRightBeneficialOwnershipExerciseThreshold" abstract="false" name="ClassOfWarrantOrRightBeneficialOwnershipExerciseThreshold" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:pureItemType"/>
  <xs:element id="mdgl_ClassOfWarrantOrRightBeneficialOwnershipMaximumThreshold" abstract="false" name="ClassOfWarrantOrRightBeneficialOwnershipMaximumThreshold" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:pureItemType"/>
  <xs:element id="mdgl_ClassOfWarrantOrRightBeneficialOwnershipExercisePercentageNoticePeriod" abstract="false" name="ClassOfWarrantOrRightBeneficialOwnershipExercisePercentageNoticePeriod" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:durationItemType"/>
  <xs:element id="mdgl_CowenCo.LlcMember" abstract="true" name="CowenCo.LlcMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="mdgl_TwoThousandAndTwentyOneSalesAgreementMember" abstract="true" name="TwoThousandAndTwentyOneSalesAgreementMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="mdgl_A2024SalesAgreementMember" abstract="true" name="A2024SalesAgreementMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="mdgl_A2024SalesAgreementAndSalesAgreementAmendmentMember" abstract="true" name="A2024SalesAgreementAndSalesAgreementAmendmentMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="mdgl_CommonStockAggregateOfferingPrice" abstract="false" name="CommonStockAggregateOfferingPrice" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="mdgl_StockPlan2015Member" abstract="true" name="StockPlan2015Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="mdgl_InducementPlan2023Member" abstract="true" name="InducementPlan2023Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="mdgl_TwoThousandAndFifteenStockAndInducementPlanMember" abstract="true" name="TwoThousandAndFifteenStockAndInducementPlanMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="mdgl_CommonStockCapitalSharesGrantedAndIssuable" abstract="false" name="CommonStockCapitalSharesGrantedAndIssuable" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:sharesItemType"/>
  <xs:element id="mdgl_EligibleToEarnPerformanceShareMember" abstract="true" name="EligibleToEarnPerformanceShareMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="mdgl_HoffmanLaRocheMember" abstract="true" name="HoffmanLaRocheMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="mdgl_ResearchDevelopmentAndCommercializationAgreementMember" abstract="true" name="ResearchDevelopmentAndCommercializationAgreementMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="mdgl_CollaborativeArrangementContingentConsiderationLiabilityMilestonePayment" abstract="false" name="CollaborativeArrangementContingentConsiderationLiabilityMilestonePayment" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="mdgl_RemainingMilestonePayments" abstract="false" name="RemainingMilestonePayments" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="mdgl_RichardLevyMember" abstract="true" name="RichardLevyMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
</xs:schema>
