To target the reactive oxygen species (ROS) accumulation and renal tubular epithelial cell (rTEC) death in renal ischemia-reperfusion injury (IRI), we constructed a nanoparticle that offers ROS scavenging and rTEC-death inhibition: mesoporous zinc-tannic acid nanozyme (ZnTA). After successfully constructing ZnTA, we proceeded to examine its effect on ROS accumulation, cellular ferroptosis and apoptosis, as well as injury severity. Malondialdehyde, Fe amounts and 4-HNE staining demonstrated that ZnTA effectively attenuated rTEC ferroptosis. TUNEL staining confirmed that Zn carried by ZnTA could effectively inhibit caspase 3 and caspase 9, mitigating apoptosis. Finally, it reduced renal IRI through the synergistic effect of ROS scavenging and cell-death inhibition. This study is expected to provide a paradigm for a combined therapeutic strategy for renal IRI.