Oxidative stress (OS) resulting from excessive reactive oxygen species (ROS) is the initial pathogenesis of many diseases, thus various pharmaceutical materials are explored to scavenge ROS. However, the medical applications of most ROS‐scavenging materials are limited due to side effects and low bio‐stability. DNA has emerged as a promising ROS‐scavenging material with excellent biosafety and programmability, but the efficiency needs to be improved by developing new fabrication methods. Here, a sub‐nanoscale TiO2 composite modified with DNA with excellent biostability, biocompatibility, and enhanced ROS‐scavenging efficiency for medical applications is presented. The sub‐nanoscale TiO2‐DNA (SNTD) composite exhibits higher scavenging capacities for multiple ROS including ·OH, H2O2, and O2•−. Additionally, it can regulate macrophages from pro‐inflammatory to anti‐inflammatory phenotype. In vivo experiments show that the nanocomposites reduce ROS concentration, decrease inflammatory cell infiltration, accelerate re‐epithelization, and promote collagen regeneration, thereby enhancing the healing of infected skin wounds.