Herein, we report that dihydrolipoic acid and lipoic acid (LA) plus lipoamide dehydrogenase and NADH denitrosate S‐nitrosocaspase 3 (CASP‐SNO). In HepG2 cells, S‐nitroso‐l‐cysteine ethyl ester (SNCEE) impeded the activity of caspase 3 (CASP‐SH), while a subsequent incubation of the cells in SNCEE‐free medium resulted in endogenous denitrosation and reactivation of CASP‐SH. The latter process was inhibited in thioredoxin reductase‐deficient HepG2 cells, in which, however, LA markedly reactivated CASP‐SH. The data obtained are discussed with focus on low molecular mass dithiols that mimic the activity of thioredoxin in reactions of protein S‐denitrosation.