Abstract Since the first report of DNAzyme by in vitro selection in 1994, catalytic DNA has investigated extensively, and their application has expanded continually in virtue of rapid advances in molecular biology and biotechnology. Nowadays, DNA is in the second prime time by way of DNA‐based hybrid catalysts and DNA metalloenzymes in which helical chirality of DNA serves to asymmetric catalysis. DNA‐based hybrid catalysts are attractive system to respond the demand of the times to pursuit green and sustainable society beyond traditional catalytic systems that value reaction efficiency. Herein, we highlight the recent advances and perspective of DNA‐based hybrid catalysts with various aspects of DNA as a versatile scaffold for asymmetric synthesis. We hope that scientists in a variety of fields will be encouraged to join and promote remarkable evolution of this interesting research.