Filed Pursuant to Rule 424(b)(5)
Registration No. 333-286955
PROSPECTUS SUPPLEMENT NO. 3
(to Prospectus dated June 24, 2025 and
Prospectus Supplements dated June 24, 2025
and June 30, 2025)

SenesTech, Inc.
Up to $7,580,675 of Common Stock
This prospectus supplement amends and supplements
certain information in the prospectus supplement, dated June 24, 2025, as amended and supplemented by the prospectus supplement no. 2,
dated June 30, 2025 (collectively, the “ATM Prospectus Supplement”), to the accompanying base prospectus, dated June 24, 2025
(the “Base Prospectus” and, collectively with the ATM Prospectus Supplement, the “Prospectus”) filed as part of
our registration statement on Form S-3 (File No. 333-286955) (the “Registration Statement”), relating to the offer, issuance
and sale of shares of our common stock, par value $0.001 per share (“Common Stock”), from time to time, pursuant to the terms of an At The Market Offering Agreement (“Sales Agreement”), dated June
20, 2024, by and between us and H.C. Wainwright & Co., LLC, as sales agent or principal (“Wainwright” or the “sales
agent”). Through the date hereof, we have sold an aggregate of $3,048,894.72 of shares of our Common Stock through the sales agent
under the Sales Agreement. This prospectus supplement should be read in conjunction with the Prospectus, and is qualified by reference
thereto, except to the extent that the information herein amends or supersedes the information contained in the Prospectus. This prospectus
supplement is not complete without, and may only be delivered or utilized in connection with, the Prospectus, and any future amendments
or supplements thereto.
Our Common Stock is listed on the Nasdaq Capital
Market (“Nasdaq”) under the symbol “SNES.” On September 23, 2025, the last reported sale price for our Common
Stock on Nasdaq was $4.59 per share.
As of the date of this prospectus supplement,
the aggregate market value of our outstanding Common Stock held by non-affiliates was $31,888,709.40, based on 5,185,333 shares of Common
Stock outstanding as of the date of this prospectus supplement, of which 5,185,156 shares are held by non-affiliates, and a price of $6.15
per share, which was the last reported sale price of our Common Stock on Nasdaq on August 4, 2025. During the 12 calendar months prior
to and including the date of this prospectus supplement, we have sold $3,048,894.72 of securities pursuant to General Instruction I.B.6
of Form S-3.
We are filing this prospectus supplement to
amend and supplement, as of September 24, 2025, the ATM Prospectus Supplement to update the maximum aggregate offering price of
shares of our Common Stock that may be offered and sold under the Registration Statement pursuant to General Instruction I.B.6 of
Form S-3. After giving effect to the $10,629,569.80 offering limit imposed by General Instruction I.B.6 of Form S-3 and
deducting amounts offered and sold pursuant to General Instruction I.B.6 of Form S-3 in the 12 calendar months prior to the date of
this prospectus supplement, we may offer and sell additional shares of our Common Stock having an aggregate offering price of up to
$7,580,675 from time to time through the sales agent in accordance with the terms of the Sales Agreement, which amount is in
addition to the aggregate of $1,036,968.48 of shares of our Common Stock previously sold pursuant to the Prospectus and in
accordance with the Sales Agreement. Pursuant to General Instruction I.B.6 of Form S-3, in no event will we sell securities pursuant
to this prospectus supplement with a value of more than one-third of the aggregate market value of our Common Stock held by
non-affiliates in any twelve-month calendar period, so long as the aggregate market value of our Common Stock held by non-affiliates
is less than $75,000,000. In the event that subsequent to the date of this prospectus supplement, the aggregate market value of our
outstanding Common Stock held by non-affiliates equals or exceeds $75,000,000, then the one-third limitation on sales shall not
apply to additional sales made pursuant to this prospectus supplement.
Investing in our securities involves a high
degree of risk. Please read “Risk Factors” beginning on page S-4 of the ATM Prospectus Supplement and other documents and
information contained or incorporated by reference in this prospectus supplement and the ATM Prospectus Supplement.
Neither the Securities and Exchange Commission
nor any state securities commission has approved or disapproved of these securities or determined if this prospectus supplement is truthful
or complete. Any representation to the contrary is a criminal offense. The securities are not being offered in any jurisdiction where
the offer is not permitted.
H.C. Wainwright & Co.
The date of this prospectus supplement is September
24, 2025.