The low catalytic efficiency of redox-active cofactor photoregeneration severely limits the performance of photoenzymatic hybrid systems. Herein, we synthesized thiophene-conjugated porous C3N4 nanosheets (CN-ATCN) exhibiting boosted photoregeneration activity of nicotinamide cofactors (NADH and NADPH), which are the most common redox cofactors of oxidoreductases, with regeneration rates of 59.00 μ M/min for NADH and 40.99 μ M/min for NADPH, ～ 84.3 and 24.7 times higher than those of bulk g-C3N4 , respectively. The thin nanosheet structure of CN-ATCN facilitates the exposure of active sites to reactants and favors the diff usion of reactants and products. Upon conjugation of a thiophene moiety into the carbon nitride framework, the optical and photoelectric properties of CN-ATCN were considerably enhanced by an extended π -conjugation system in the frameworks and molecular type II heterojunctions formed between the incorporated and non-incorporated portions of CN-ATCN. Upon coupling NAD(P)H photoregeneration reaction by CN-ATCN with NAD(P) H-dependent enzymatic systems, sustainable synthesis of L-tert-leucine and styrene oxide was achieved with rates of 964 and 14.9 μ M/h, respectively.