Nanozymes are nanomaterials with enzymatic properties designed to overcome the inherent limitations of natural enzymes. They can mimic various enzyme activities with durability, low cost, and tunable catalytic properties. With the rapid development of nanotechnology, biotechnology, catalytic science, and computational chemistry, remarkable progress has been made in the research of nanozymes. However, compared with natural enzymes, the reported nanozymes possess lower catalytic activity, which limits their further application. Single-atom nanozymes (SAzymes) are a new type of nanozymes that have been widely explored in recent years. With their maximum active site density and well-defined coordination environment, SAzymes have demonstrated excellent catalytic performance, showing broad application prospects in many fields such as biosensing, antibacterial, and tumor therapy. Furthermore, the well-defined atomic coordination and electron configuration of SAzymes provide strong support to reveal the complex mechanism of their catalytic reaction. Particularly, the noble metal-based SAzymes precisely synthesized on the atomic scale, inherit the advantages of SAzymes, while combining the excellent electronic conductivity, high stability and good catalytic activity of noble metals. This effectively reduces the production cost and gives the noble metal-based SAzymes a great potential for practical applications. In this review, we focus on the recent advances of noble metal-based SAzymes in biomedicine and discuss their underlying challenges as well as future prospects.