Acute kidney injury (AKI) is a sudden kidney dysfunction caused by aberrant reactive oxygen species (ROS) metabolism that results in high clinical mortality. The rapid development of ROS scavengers provides new opportunities for AKI treatment. Herein, the use of hydrogen-terminated germanene (H-germanene) nanosheets is reported as an antioxidative defense nanoplatform against AKI in mice. The simulation results show that 2D H-germanene can effectively scavenge ROS through free radical adsorption and subsequent redox reactions. In particular, the H-germanene exhibits high accumulation in injured kidneys, thereby offering a favorable opportunity for treating renal diseases. In the glycerol-induced murine AKI model, H-germanene delivers robust antioxidative protection against ROS attack to maintain normal kidney function indicators without negative influence in vivo. This positive in vivo antioxidative defense in living animals demonstrates that the present H-germanene nanoplatform is a powerful antioxidant against AKI and various anti-inflammatory diseases.