Inspired by water-forming NAD(P)H oxidases, a cooperative photobiocatalytic system has been designed to aerobically regenerate the oxidized nicotinamide cofactors. Photocatalysts enable NAD(P)H oxidation with O₂ under visible-light irradiation, producing H₂ O₂ as a byproduct, which is subsequently used as an oxidant by the horseradish peroxidase mediator system (PMS) to oxidize NAD(P)H. The photobiocatalytic system shows a turnover frequency of 8800 min^-1 in the oxidation of NAD(P)H. Photobiocatalytic NAD(P)H oxidation proceeds smoothly at pH 6-9. In addition to natural NAD(P)H, synthetic biomimetics are also good substrates for this regeneration system. Total turnover numbers of up to 180000 are obtained for the cofactor when the photobiocatalytic regeneration system is coupled with dehydrogenase-catalyzed oxidations. It may be a promising protocol to recycle the oxidized cofactors for catalytic oxidations.