AbstractSurface decontamination is a crucial step in the treatment of peri‐implant infections, yet deep and mild cleansing techniques are lacking. Drawing inspiration from lysosomes, which enclose hydrolytic enzymes within their membranes to safely and effectively degrade organics within cells, the use of a near‐infrared (NIR)/H2O2‐activated TiO2‐x‐Alginate system for enclosed and deep surface decontamination is proposed. It leverages synergistically generated reactive oxygen species (ROS) to eliminate bacterial contaminants, mimicking the process of lysosomal digestion. By employing Ca2+ spray‐induced surface gelation, the TiO2‐x and H2O2 around implant surface are enclosed, creating a membrane‐like isolation. This system robustly degrades extracellular polymeric substances (EPS)‐mimic biomacromolecules, removes organic residues (OR) from both mono‐species (Staphylococcus aureus and Porphyromonas gingivalis) biofilm and polymicrobial ex vivo biofilm of peri‐implantitis, while avoiding healthy tissue irritation. Encouragingly, this system has also demonstrated powerful decontamination capabilities when applied to clinic‐retrieved infected dental implants. Notably, this technique restores the pristine implant surface topography and chemical composition, which are further revealed by the minimal inflammation response observed in macrophage culture and subcutaneous implantation. Consequently, osteoblast functionalities are effectively restored, and re‐osseointegration in vivo is also greatly enhanced. Thus, this deep decontamination strategy holds great promise for clinical applications in managing peri‐implant infections.