The abuse of antibiotics makes bacterial infection an increasingly serious global health threat. Reactive oxygen species (ROS) are the ideal alternative antibacterial approach for quick and effective sterilization. Although various antibacterial strategies based on ROS have been developed, many of them are still limited by insufficient antibacterial efficiency. Here, we have developed an acid-enhanced dual-modal antibacterial strategy based on zeolitic imidazolate frameworks-8 (ZIF8) -derived nanozyme. ZIF8, which can release Zn, is chosen as the carrier to integrate glucose oxidase (GOx) and gold nanoparticles (Au NPs) which can produce ROS via a cascade catalytic reaction. Thus, the bactericidal capability of ROS and Zn have been integrated. More importantly, gluconic acid, a "by-product" of the catalytic reaction, can generate an acidic environment to promote both the ROS-producing and Zn-releasing, enhancing the overall antibacterial performance further. This triple-synergistic strategy exhibits extraordinary bactericidal ability at a low dosage of 4 μg/mL (for ) and 8 μg/mL (for ), which shows a great potential of MOF-derived nanozyme for efficient bacterial eradication and diverse biomedical applications.