Modulating the electronic structure of supported metal nanoparticles through rational catalyst design has emerged as an effective strategy for enhancing electrocatalytic performance, yet the interplay between metal nanoparticles and carbon supports in boosting reactive oxygen species (ROS) electrosynthesis remains poorly understood. Here, we report a strategy to achieve highly efficient ROS electrosynthesis with graphdiyne (GDY)-supported palladium-platinum nanoparticles (PdPt/GDY) as the catalyst. PdPt/GDY is prepared by successive electroless deposition of Pd and Pt. With the PdPt/GDY as the catalyst, the electrochemical synthetic system produces substantially more ROS from hydrogen peroxide (H₂O₂) reduction reaction (HPRR) compared with those with PdPt nanoparticles supported onto other carbon-based nanomaterials as the catalysts. Operando luminol electrochemiluminescence (ECL) characterization and theoretical calculation reveal the origin of the high efficiency for ROS synthesis, which stems from the synergistic Pd-Pt atomic interactions and strong coupling of metal nanoparticles with alkyne-rich GDY. The high efficiency of PdPt/GDY for ROS electrosynthesis enables superior perfluorooctanoic acid degradation and defluorination among all carbon-supported PdPt analogues, highlighting its high capability for the deep degradation of persistent fluorinated pollutants. This work establishes a framework for rational catalyst design for sustainable ROS electrosynthesis with appealing environmental applications.