Nanozymes, nanomaterials possessing enzymatic activity, have been studied extensively by researchers. However, their complex composition, low density of active sites, and inadequate substrate selectivity have hindered the maturation and widespread acceptance of nanozymes. Single-atom nanozymes (SAzymes) with atomically dispersed active sites are leading the field of catalysis due to their exceptional performance. The maximum utilization rate of atoms, low cost, well-defined coordination structure, and active sites are the most prominent advantages of SAzymes that researchers favor. This review systematically categorizes SAzymes based on their support type and describes their specific applications. Additionally, we discuss regulation strategies for SAzyme activity and provide a comprehensive summary of biosafety challenges associated with these enzymes.