In enzymology, a 2,5-didehydrogluconate reductase (EC 1.1.1.274) is an enzyme that catalyzes the chemical reaction

2-dehydro-D-gluconate + NADP⁺ ${\displaystyle \rightleftharpoons }$ 2,5-didehydro-D-gluconate + NADPH + H⁺

Thus, the two substrates of this enzyme are 2-dehydro-D-gluconate and NADP⁺, whereas its 3 products are 2,5-didehydro-D-gluconate, NADPH, and H⁺.

This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD⁺ or NADP⁺ as acceptor. The systematic name of this enzyme class is 2-dehydro-D-gluconate:NADP⁺ 2-oxidoreductase. Other names in common use include 2,5-diketo-D-gluconate reductase, and YqhE reductase.

As of late 2007, only one structure has been solved for this class of enzymes, with the PDB accession code 1VP5.