<?xml version="1.0"?>
<ownershipDocument>

    <schemaVersion>X0609</schemaVersion>

    <documentType>4</documentType>

    <periodOfReport>2026-06-11</periodOfReport>

    <issuer>
        <issuerCik>0001840233</issuerCik>
        <issuerName>Xilio Therapeutics, Inc.</issuerName>
        <issuerTradingSymbol>XLO</issuerTradingSymbol>
        <issuerForeignTradingSymbol></issuerForeignTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001733077</rptOwnerCik>
            <rptOwnerName>ROSS ROBERT W.</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerNonUSAddressFlag>false</rptOwnerNonUSAddressFlag>
            <rptOwnerStreet1>828 WINTER STREET</rptOwnerStreet1>
            <rptOwnerStreet2>SUITE 300</rptOwnerStreet2>
            <rptOwnerCity>WALTHAM</rptOwnerCity>
            <rptOwnerState>MA</rptOwnerState>
            <rptOwnerZipCode>02451</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>true</isDirector>
            <isOfficer>false</isOfficer>
            <isTenPercentOwner>false</isTenPercentOwner>
            <isOther>false</isOther>
        </reportingOwnerRelationship>
    </reportingOwner>

    <aff10b5One>false</aff10b5One>

    <derivativeTable>
        <derivativeTransaction>
            <securityTitle>
                <value>Stock Option (right to buy)</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>7.99</value>
            </conversionOrExercisePrice>
            <transactionDate>
                <value>2026-06-11</value>
            </transactionDate>
            <transactionCoding>
                <transactionFormType>4</transactionFormType>
                <transactionCode>A</transactionCode>
                <equitySwapInvolved>false</equitySwapInvolved>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>5000</value>
                </transactionShares>
                <transactionPricePerShare>
                    <value>0</value>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>A</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <exerciseDate>
                <footnoteId id="F1"/>
            </exerciseDate>
            <expirationDate>
                <value>2036-06-10</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>5000</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>5000</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeTransaction>
    </derivativeTable>

    <footnotes>
        <footnote id="F1">The option was granted on June 11, 2026 and will vest as to 100% of the shares underlying the option on the earlier of (i) June 11, 2027 and (ii) the Issuer's next annual meeting of stockholders following the grant date, subject to the Reporting Person's continued service to the Issuer through the vesting date.</footnote>
    </footnotes>

    <ownerSignature>
        <signatureName>/s/ Christopher Frankenfield, Attorney-in-Fact</signatureName>
        <signatureDate>2026-06-12</signatureDate>
    </ownerSignature>
</ownershipDocument>
