In enzymology, a 2-dehydro-3-deoxy-D-gluconate 5-dehydrogenase (EC 1.1.1.127) is an enzyme that catalyzes the chemical reaction

2-dehydro-3-deoxy-D-gluconate + NAD⁺ ${\displaystyle \rightleftharpoons }$ (4S)-4,6-dihydroxy-2,5-dioxohexanoate + NADH + H⁺

Thus, the two substrates of this enzyme are 2-dehydro-3-deoxy-D-gluconate and NAD⁺, whereas its 3 products are (4S)-4,6-dihydroxy-2,5-dioxohexanoate, NADH, and H⁺.

This enzyme participates in pentose and glucuronate interconversions.

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-3-deoxy-D-gluconate:NAD⁺ 5-oxidoreductase. Other names in common use include 2-keto-3-deoxygluconate 5-dehydrogenase, 2-keto-3-deoxy-D-gluconate dehydrogenase, 2-keto-3-deoxygluconate (nicotinamide adenine dinucleotide, (phosphate)) dehydrogenase, 2-keto-3-deoxy-D-gluconate (3-deoxy-D-glycero-2,5-hexodiulosonic, and acid) dehydrogenase.