Nature has evolved enzymes with exquisite active sites that

catalyze biotransformations with high efficiency. However, the

exploitation of natural enzymes is often hampered by poor stability, and

natural enzyme production and purification are costly. Supramolecular

self‐assembly allows the construction of biomimetic active sites,

although it is challenging to produce such artificial enzymes with

catalytic activity and stability that rival those of natural enzymes. We

report herein a strategy to produce a horseradish peroxidase (HRP)

mimic based on the assembly of chitosan with a G‐quadruplex DNA

(G‐DNA)/hemin complex. A network‐like morphology of the assembled

nanomaterial was observed together with a remarkable enhancement of

peroxidase activity induced by the chitosan and G‐DNA components. The

turnover frequency and catalytic efficiency of the enzyme‐mimicking

material reached or even surpassed those of HRP. Moreover, the catalytic

complex exhibited higher tolerance than HRP to harsh environments, such

as extremely low pH or high temperatures. In accord with the

experimental and simulated results, it is concluded that the spatial

distribution of the G‐DNA and chitosan components and the exposure of

the catalytic center may facilitate the coordination of substrates by

the hemin iron, leading to the superior activity of the material. Our

work provides a simple and affordable avenue to produce highly active

and robust enzyme‐mimicking catalytic nanomaterials.