Bioinspired and biosafety antioxidant nanoparticle assemblies from natural occurring molecules have been regarded as a class of effective therapeutic nanomaterials for addressing current inflammatory diseases such as acute kidney injury. In this study, a series of epicatechin-assembled nanoparticles have been developed via one-pot enzymatic polymerization of epicatechin. The prepared poly (epicatechin) (PEC) nanoparticles (NPs) showed excellent antioxidant capacity to scavenge multiple toxic free radicals, thus being able to effectively protect cells under oxidative stress conditions in vitro. Furthermore, in the renal ischemia/reperfusion model, blood renal function testing and renal tissue staining revealed a prominent therapeutic effect of PEC NPs. All these findings suggested that this class of bioinspired antioxidant nanoparticles provided a new therapeutic strategy for human ischemia/reperfusion-related diseases.