Developing high-efficiency artificial biocatalysts for scavenging reactive oxygen species (ROS) is critical for treating inflammation diseases and promoting tissue regeneration. By mimicking the active sites in catalase, here, a Pt-clusters-equipped antioxidase-like biocatalysts (Pt─CN) with superior catalytic abilities for stem cell protection and periodontitis treatment are reported. Owing to the excellent effects of multiple Pt clusters, Pt─CN yields exceptional catalytic ROS-scavenging activities for multiple types of ROS. In vitro studies show that Pt─CN can effectively protect stem cell survival, adhesion, and differentiation in a high ROS levels microenvironment. Additionally, Pt─CN can reduce the M1/M2 ratio of macrophages when stimulated by lipopolysaccharide. In vivo treatment of mouse periodontitis further confirms the protection against bone loss and reduction in the inflammatory response. This study provides a basis for the application of biocatalysts with Pt catalytic center in macrophage polarization, stem cell protection, and periodontitis treatment, thus offering a new strategy for the design of high-performance artificial biocatalysts.