Enzyme cascade reactions that integrate natural enzymes and nanozymes have attracted intensive attention in biomedical studies. Nevertheless, it is still an important challenge to design simple, high-performance and safe cascade reaction systems. Herein, we constructed a cascade reactor Pd-Ru/GOx, in which two-dimensional Pd-Ru nanosheets (NSs) with excellent peroxidase (POD)-like activity were employed as a carrier for the covalent grafting of glucose oxidase (GOx) by glutaraldehyde coupling chemistry. The designed Pd-Ru/GOx cascade reactor possesses both GOx and POD-like activities and can not only transform non-toxic glucose into toxic hydroxyl radicals (˙OH) but also decrease the pH value of the reaction system to improve catalytic activity, achieving dual effects of cascade synergy and promotion. The in vitro and vivo experimental results manifested that Pd-Ru/GOx presented good antibacterial effects via the generation of reactive oxygen species (ROS). This work offers a simple strategy to construct a highly efficient and safe enzymatic cascade nanoreactor and holds tremendous promise for clinical bacterial infection control.