In enzymology, a protein-disulfide reductase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are protein dithiol, NAD<sup>+</sup>, and NADP<sup>+</sup>, whereas its 4 products are protein disulfide, NADH, NADPH, and H<sup>+</sup>.
This enzyme belongs to the family of oxidoreductases, specifically those acting on a sulfur group of donors with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is protein-dithiol:NAD(P)+ oxidoreductase. Other names in common use include protein disulphide reductase, insulin-glutathione transhydrogenase, disulfide reductase, and NAD(P)H2:protein-disulfide oxidoreductase.
As of late 2007, 8 structures have been solved for this class of enzymes, with PDB accession codes , , , , , , , and .