Abstract While antioxidant therapies targeting reactive oxygen species (ROS) overproduction and inflammation hold clinical promise, developing effective and durable nanozymes remains challenging. To address this, a highly efficient copper single‐atom nanozyme (Cu SA /TiO 2‐x ) is engineered, exhibiting robust superoxide dismutase‐like activity and significant glutathione peroxidase‐like functionality. This dual‐action design enabled efficient ROS scavenging and consequent suppression of inflammation in lipopolysaccharide‐stimulated macrophages. Crucially, the presence of Ti 3+ in TiO 2‐x support enhances the stabilization of Cu SA /TiO 2‐x by promoting the reduction of Cu 2+ ions to Cu + ions, thereby facilitating robust metal immobilization. Moreover, SAzyme catalytic activity is systematically modulated through metal selection and loading control, achieving effective tuning of enzyme‐like activity across different metal‐SAzyme systems. This innovative synthesis and application of Cu SA /TiO 2‐x offers a promising strategy for the controlled synthesis of TiO 2 ‐based SAzymes and advances their potential in medical applications.