Exhibit 5.1

April 26, 2021

Protagenic Therapeutics Inc.

149 Fifth Avenue, Suite 500

New York, NY 10010

Ladies and Gentlemen:

We have acted as special counsel to the Company, a corporation incorporated under the laws of the State of Delaware, in connection with the preparation and filing by the Company with the Securities and Exchange Commission (the “Commission”) pursuant to Rule 462(b) under the Securities Act of 1933, as amended (the “Securities Act”), of a registration statement on Form S-1 (the “462(b) Registration Statement”) relating to the registration under the Securities Act of the offer and sale by the Company of up to 609,500 units of the Company, including the underwriters’ option to purchase an additional 79,500 units (collectively, the “Units”), with each Unit consisting of one share of the Company’s common stock, par value $0.0001 per share, (the “Common Stock”, such shares of Common Stock, the “Shares”), and one warrant representing the right to purchase one additional share of Common Stock (the “Warrants”) in an aggregate amount equal to the number of the Shares (the “Warrant Shares”), and the issuance of the Warrant Shares upon exercise of the Warrants. The Shares, the Warrants, and the Warrant Shares are collectively referred to herein as the “Securities.” The 462(b) Registration Statement relates to the Company’s registration statement on Form S-1, as amended (File No. 333-253006) (the “Registration Statement”), initially filed by the Company on February 11, 2021 and declared effective by the Commission on April 26, 2021.

In that connection, we have examined originals, or copies certified or otherwise identified to our satisfaction, of such documents, corporate records and other instruments as we have deemed necessary for the purposes of this opinion, including (i) the Third Amended and Restated Certificate of Incorporation of the Company in the form filed as Exhibit 3.1 to the Registration Statement, as filed with the Secretary of State of the State of Delaware on June 15, 2016 (the “Certificate of Incorporation”); (ii) the Second Amended and Restated Bylaws of the Company in the form filed as Exhibit 3.3 to the Registration Statement, as filed with the Commission on June 1, 2018; (iii) the Underwriting Agreement in the form filed as Exhibit 1.1 to the Registration Statement (the “Underwriting Agreement”); (iv) resolutions of the board of directors of the Company; (v) the form of Warrant Agreement proposed to be entered into between the Company and American Stock Transfer & Trust Company, LLC, as warrant agent (the “Warrant Agreement”), filed as Exhibit 10.15 to the Registration Statement; (vi) the form of Warrant, filed as Exhibit 4.5 to the Registration Statement; and (vii) the Registration Statement and the 462(b) Registration Statement.

Protagenic Therapeutics Inc.
April 26, 2021 Page 2

For purposes of this opinion, we have assumed the authenticity of all documents submitted to us as originals, the conformity to the originals of all documents submitted to us as copies and the authenticity of the originals of all documents submitted to us as copies. We have also assumed the legal capacity of all natural persons, the genuineness of the signatures of persons signing all documents in connection with which this opinion is rendered, the authority of such persons signing on behalf of the parties thereto and the due authorization, execution and delivery of all documents by the parties thereto other than the Company. We have not independently established or verified any facts relevant to the opinion expressed herein, but have relied upon statements and representations of officers and other representatives of the Company and others as to factual matters.

Based upon and subject to the foregoing qualifications, assumptions and limitations and the further limitations set forth below, we are of the opinion that, upon (i) due action by the board of directors of the Company or a duly appointed committee thereof to determine the price per share of the Shares, (ii) the due execution and delivery of the Underwriting Agreement by the parties thereto, (iii) the effectiveness of the Registration Statement under the Securities Act and such effectiveness shall not have been terminated or rescinded,

(i) when the 462(b) Registration Statement becomes effective under the Securities Act, the Shares will have been duly authorized and, when issued upon receipt by the Company of the consideration therefore, will be validly issued, fully paid and non-assessable;

(ii) when the 462(b) Registration Statement becomes effective under the Securities Act, the Warrants will have been duly authorized and, when duly executed and delivered by the Company in the manner and for consideration therefor, will constitute valid and legally binding obligations of the Company; and

(iii) the Warrant Shares, if and when issued, paid for and delivered in compliance with the terms of the Warrants and in compliance with the terms of the Company’s Certificate of Incorporation as in effect from time to time, will be validly issued, fully paid and non-assessable.

The foregoing opinions are qualified to the extent that the enforceability of any document, instrument or the Warrants may be limited by or subject to bankruptcy, insolvency, fraudulent transfer or conveyance, reorganization, moratorium or other similar laws relating to or affecting creditors’ rights generally, and general equitable or public policy principles.

Our opinions expressed above are subject to the qualifications that we express no opinion as to the applicability of, compliance with, or effect of any laws except the General Corporation Law of the State of Delaware.

We hereby consent to the filing of this opinion with the Commission as Exhibit 5.1 to the 462(b) Registration Statement. We also consent to the reference to our firm under the heading “Legal Matters” in the prospectus forming part of the Registration Statement or any prospectus filed pursuant to Rule 424(b) with respect thereto. In giving this consent, we do not thereby admit that we are in the category of persons whose consent is required under Section 7 of the Securities Act or the rules and regulations of the Commission.

Protagenic Therapeutics Inc.
April 26, 2021 Page 3

We do not find it necessary for the purposes of this opinion, and accordingly we do not purport to cover herein, the application of the securities or “Blue Sky” laws of the various states to the offering of the Securities pursuant to the Registration Statement.

This opinion letter is given to you solely for use in connection with the offer and sale of the Securities while the Registration Statement or 462(b) Registration Statement is in effect and is not to be relied upon for any other purpose. This opinion is limited to the specific issues addressed herein, and no opinion may be inferred or implied beyond that expressly stated herein. We assume no obligation to revise or supplement this opinion should the General Corporation Law of the State of Delaware be changed by legislative action, judicial decision or otherwise.