Nanozymes with intrinsic enzyme-mimicking activities have shown great potential to become surrogates of natural enzymes in many fields by virtue of their advantages of high catalytic stability, ease of functionalization, and low cost. However, due to the lack of predictable descriptors, most of the nanozymes reported in the past have been obtained mainly through trial-and-error strategies, and the catalytic efficacy, substrate specificity, as well as practical application effect under physiological conditions, are far inferior to that of natural enzymes. To optimize the catalytic efficacies and functions of nanozymes in biomedical settings, recent studies have introduced biosystem-inspired strategies into nanozyme design. In this review, recent advances in the engineering of biosystem-inspired nanozymes by leveraging the refined catalytic structure of natural enzymes, simulating the behavior changes of natural enzymes in the catalytic process, and mimicking the specific biological processes or living organisms, are introduced. Furthermore, the currently involved biomedical applications of biosystem-inspired nanozymes are summarized. More importantly, the current opportunities and challenges of the design and application of biosystem-inspired nanozymes are discussed. It is hoped that the studies of nanozymes based on bioinspired strategies will be beneficial for constructing the new generation of nanozymes and broadening their biomedical applications.