In situ growth of MnO2 nanoparticles (NPs) onto chiral P/M-polyaniline (P/M-PANI) scaffolds efficiently regulates the supramolecular chirality, making them function as chiral nanozymes for controllable enantioselective catalysis. Compared with the ex situ loaded MnO2 NPs onto P/M-PANI scaffolds, the enantioselectivity of the in situ growth system is significantly enhanced due to the stronger bonding between catalytic centers and supramolecular scaffolds.