Form S-8 Design Therapeutics,

Exhibit 5.1

 

Kenneth J. Rollins

+1 858
550 6136

[email protected]

March 26, 2021

Design Therapeutics, Inc.

6005 Hidden Valley Road, Suite 110

Carlsbad, CA 92011

Ladies and Gentlemen:

We have represented Design Therapeutics, Inc., a Delaware corporation (the “Company”), in connection with the filing by the Company of
a registration statement on Form S-8 (the “Registration Statement”) with the Securities and Exchange Commission, covering the offering of up to 11,788,238 shares (the
“Shares”) of the Company’s common stock, par value $0.0001 per share (the “Common Stock”), consisting of (i) 1,806,733 shares of Common Stock issuable pursuant to the Company’s 2018 Equity
Incentive Plan (the “Prior Plan”), (ii) 9,381,505 shares of Common Stock issuable pursuant to the Company’s 2021 Equity Incentive Plan (the “2021 Plan”), and (iii) 600,000 shares of Common Stock issuable
pursuant to the Company’s 2021 Employee Stock Purchase Plan (together with the Prior Plan and the 2021 Plan, the “Plans”). .

In connection with this opinion, we have examined and relied upon (i) the Registration Statement and the related prospectuses, (ii) the
Company’s Amended and Restated Certificate of Incorporation, as amended, and Bylaws, each as currently in effect, (iii) the forms of the Company’s Amended and Restated Certificate of Incorporation and Amended and Restated Bylaws, each
of which is to be in effect upon the closing of the Company’s initial public offering in the forms filed as Exhibits 3.2 and 3.4, respectively, to the Company’s registration statement (No.
333-253954) on Form S-1, (iv) the Plans, and (v) originals or copies certified to our satisfaction of such records, documents, certificates, memoranda and other
instruments as in our judgment are necessary or appropriate to enable us to render the opinion expressed below.

We have assumed the genuineness of all
signatures, the authenticity of all documents submitted to us as originals, the conformity to originals of all documents submitted to us as copies, the accuracy, completeness and authenticity of certificates of public officials and the due
authorization, execution and delivery by all persons other than by the Company of all documents where authorization, execution and delivery are prerequisites to the effectiveness thereof. As to certain factual matters, we have relied upon a
certificate of an officer of the Company and have not independently verified such matters.

Our opinion is expressed only with respect to the General
Corporation Law of the State of Delaware. We express no opinion to the extent that any other laws are applicable to the subject matter hereof and express no opinion and provide no assurance as to compliance with any federal or state securities law,
rule or regulation.

On the basis of the foregoing, and in reliance thereon, we are of the opinion that the Shares, when sold and issued in accordance
with the Plans, the Registration Statement and related prospectuses, will be validly issued, fully paid and nonassessable (except as to shares issued pursuant to certain deferred payment arrangements, which will be fully paid and nonassessable when
such deferred payments are made in full).

Cooley LLP    4401 Eastgate Mall    San Diego,
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