Nanozymes have been widely used as highly active and stable arterial enzymes due to their controllable electronic transfer and unique catalytic reaction route. However, the development of nanozymes is hindered by their ambiguous structure, insufficient activity and inadequate substrate selectivity. In comparison, single-atom nanozymes (SAzymes) hold superior catalytic activity 10-100 times higher than conventional nanozymes by maximizing the utilization of metal atom dispersion, and exhibit versatile catalytic selectivity through precisely adjusting the atom spatial configuration. In this review, we highlight several well-defined SAzymes, and discuss their accurate atom configuration, catalytic mechanisms, enzyme-like activity, and applications in cancer treatment, brain disease, and wound healing. It is of great significance to understand the advantages and properties of SAzymes for further medical development.