The research on nanozymes has increased dramatically in recent years and a new interdiscipline, nanozymology, has emerged. A variety of nanomaterials have been designed to mimic the characteristics of natural enzymes, which connects an important bridge between nanotechnology and biological science. Unlike natural enzymes, the nanoscale properties of nanozymes endow them with the potential to regulate their enzymatic-like activity from different perspectives. The mechanisms behind those methods are intriguing. In this Review, we introduce these mechanisms from the aspects of surface chemistry, surface modification, molecular imprinting, and hybridization and then focus attention on some specific catalytic mechanisms of several representative nanozymes. The applications of nanozymes ranging from bioassay, imaging, to disease therapy are also discussed in detail to prove the fact that the inherent physicochemical properties of nanomaterials not only make nanozymes the analogues of biological enzymes, but also endow them with incomparable advantages and broad prospects in biomedical fields. Finally, four characteristics and some challenges of nanozymes are summarized.