Xilio Therapeutics, Inc.

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

SCHEDULE 14A

Proxy Statement Pursuant to Section 14(a) of the

Securities Exchange Act of 1934

(Amendment No. )

Filed by the Registrant☒

Filed by a Party other than the Registrant☐

Check the appropriate box:

XILIO THERAPEUTICS, INC.

(Name of registrant as specified in its charter)

(Name of person(s) filing proxy statement, if other than the registrant)

Payment of Filing Fee (Check the appropriate box):

NOTICE OF 2026 ANNUAL MEETING OF STOCKHOLDERS

To Be Held on June 10, 2026

Dear Stockholders:

You are cordially invited to attend the 2026 annual meeting of stockholders of Xilio Therapeutics, Inc. to be held on June 10, 2026 at 11:00 a.m., Eastern Daylight Time, virtually at www.virtualshareholdermeeting.com/XLO2026.

At the annual meeting, stockholders will consider and vote on the following matters:

The election of four Class II directors nominated by our board of directors, each to serve for a three-year term expiring at the 2029 annual meeting of stockholders or until his or her successor has been duly elected and qualified;

The ratification of the selection of Ernst & Young LLP as our independent registered public accounting firm for the fiscal year ending December 31, 2026;

The approval of our Amended and Restated 2021 Stock Incentive Plan; and

The transaction of any other business that may properly come before the annual meeting or any adjournment or postponement thereof.

We have elected to provide access to our proxy materials over the internet under the U.S. Securities and Exchange Commission’s, or the SEC’s, “notice and access” rules. We believe that providing our proxy materials over the internet expedites stockholders’ receipt of proxy materials, lowers costs and reduces the environmental impact of our annual meeting. Accordingly, on or about April 28, 2026, we are sending to our stockholders a notice of internet availability of proxy materials, or the notice of availability, instead of a paper copy of our proxy materials.

Only stockholders of record at the close of business on April 16, 2026, the record date for the annual meeting, are entitled to notice of and to vote at the annual meeting or any adjournment or postponement thereof. As noted above, our annual meeting will be a virtual meeting of stockholders, which will be conducted exclusively via the internet as a virtual web conference. You will be able to attend the annual meeting online, vote your shares during the annual meeting and submit questions for consideration during the annual meeting throughwww.virtualshareholdermeeting.com/XLO2026. Please carefully review the enclosed proxy statement and the notice of availability for additional details.

Your vote is important, and we encourage all stockholders to attend the annual meeting online. Whether or not you plan to attend the annual meeting online, we encourage you to read this proxy statement and submit your proxy or voting instructions as soon as possible by following the instructions in the notice of availability and submitting your proxy by the internet, telephone, or by signing, dating and returning your proxy card or voting instruction form. Please review the instructions on each of youro voting options described in the attached proxy statement. Further information about how to register for and attend the annual meeting online, vote your shares and submit questions for consideration at the meeting is included in the accompanying proxy statement.

Thank you for your ongoing support and continued interest in Xilio Therapeutics, Inc.

By Order of the Board of Directors,

René Russo, Pharm.D.

President and Chief Executive Officer

Waltham, Massachusetts

April 28, 2026