PROSPECTUS SUPPLEMENT NO. 1(to the prospectus dated November 22, 2024) Cadrenal Therapeutics, Inc. 590,001 Shares of Common Stock This prospectus supplement updates, amends and supplements the prospectus contained in the Registration Statement on Form S-3,declared effective as of November 22, 2024 (as supplemented or amended from time to time, the “Prospectus”) (Registration No. 333-283226) relating to the resale from time to time of up to 590,001 shares of common stock, par value $0.001 per share (the “CommonStock”), of Cadrenal Therapeutics, Inc. (the “Company”), including, in part, 571,430 shares of Common Stock issuable upon theexercise of common warrants to purchase shares of Common Stock (the “Existing Warrants”) purchased by an investor in a privateplacement transaction that closed on or about November 4, 2024 (the “Private Placement”). This prospectus supplement is being filedin connection with an amendment to certain of the Existing Warrants as described below under “Amendments to Existing Warrants.”Capitalized terms used in this prospectus supplement and not otherwise defined herein have the meanings specified in the Prospectus. This prospectus supplement is not complete without the Prospectus. This prospectus supplement should be read in conjunction withthe Prospectus, which is to be delivered with this prospectus supplement, and is qualified by reference thereto, except to the extent thatthe information in this prospectus supplement updates or supersedes the information contained in the Prospectus. Please keep thisprospectus supplement with your Prospectus for future reference. Our shares of Common Stock are listed on the Nasdaq Capital Market under the symbol “CVKD”. On March 31, 2026, the closingprice for our shares of Common Stock on the Nasdaq Capital Market was $5.12 per share. Investing in our securities involves a high degree of risk. Before deciding whether to invest in our securities, you shouldconsider carefully the risks and uncertainties under the heading “Risk Factors” beginning on page 5 of the Prospectus. Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of thesesecurities or passed upon the adequacy or accuracy of the Prospectus or this prospectus supplement. Any representation to thecontrary is a criminal offense. AMENDMENTS TO EXISTING WARRANTS This prospectus supplement is being filed to disclose the following: On March 31, 2026, we entered into an amendment with a holder of Existing Warrants to purchase up to 571,430 shares of CommonStock held in the aggregate by such holder in order to amend the exercise price under such Existing Warrants from $16.50 to $4.50 pershare. The date of this prospectus supplement is April 1, 2026.