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Exhibit 23.1

CONSENT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM

We consent to the incorporation by reference in the following Registration Statements:

(1)Registration Statements (Form S-8 Nos. 333-41532, 333-168678, 333-183020, 333-210145, 333-217873, 333-234569, 333-240169, 333-258568, 333-273683, and 333-289310) pertaining to the 2017 Equity Incentive Plan and to the 2017 Non-Employee Directors’ Equity Incentive Plan of Lexicon Pharmaceuticals, Inc., and

(2)Registration Statement (Form S-3 No. 333-281208) of Lexicon Pharmaceuticals, Inc.;

of our report dated March 5, 2026, with respect to the consolidated financial statements of Lexicon Pharmaceuticals, Inc., included in this Annual Report (Form 10-K) of Lexicon Pharmaceuticals, Inc. for the year ended December 31, 2025.

/s/ Ernst & Young LLP

Houston, Texas

March 5, 2026