Acute kidney injury (AKI) is a common clinical syndrome characterized by the rapid loss of renal filtration function. No standard therapeutic agent option is currently available. The development and progression of AKI is a continuous and dynamical pathological process. Oxidative stress and inflammatory responses are the primary influencing factors. Here, we developed a biomimetic nano-system (MM-PtNCs) with reactive oxygen species (ROS)-responsive platinum nanozyme clusters (PtNCs) wrapped in macrophage membrane (MM) to alleviate AKI by modulating oxidative stress and inflammation. The inflammatory cytokines receptors retained on MM surface allowed the biomimetic nano-system to target renal inflammation and neutralize these pro-inflammatory cytokines to ameliorate inflammation. PtNCs exhibit free radical scavenging-ability and catalase (CAT)-like activity to scavenge ROS and regulate the oxidative stress situations both in injured cells and tissues. Meanwhile, it could responsively dissociate into ultrasmall platinum nanoparticles under AKI-specific ROS conditions to eliminate ROS and eventually excreted through the renal filtration system. In a mouse model of ischemia/reperfusion-induced AKI, systemic injection of MM-PtNCs significantly reduced renal damage and restored kidney function. Additionally, MM-PtNCs effectively prevented the progression of AKI to chronic kidney disease. In conclusion, MM-PtNCs may propose a multi-faceted regulatory approach for clinical AKI treatment.