SummaryExcessive reactive oxygen species (ROS) in joints could lead to gradual degeneration of the extracellular matrix (ECM) and apoptosis of chondrocytes, contributing to the occurrence and development of osteoarthritis (OA). Mimicking natural enzymes, polydopamine (PDA)-based nanozymes showed great potential in treating various inflammatory diseases. In this work, PDA loaded with ultra-small palladium (PDA-Pd) nanoparticles (NPs) was employed to scavenge ROS for OA therapy. As a result, PDA-Pd effectively declined the intracellular ROS levels and exhibited efficient antioxidative and anti-inflammatory capacity with good biocompatibility in IL-1β stimulated chondrocytes. Significantly, assisted with near-infrared (NIR) irradiation, its therapeutic effect was further enhanced. Further, NIR-stimulated PDA-Pd suppressed the progression of OA after intra-articular injection in the OA rat model. With favorable biocompatibility, PDA-Pd exhibits efficient antioxidative and anti-inflammatory capacity, leading to the alleviation of OA in rats. Our findings may provide new insights into the treatment of various ROS-induced inflammatory diseases.