Cisplatin-associated acute kidney injury (AKI) is a severe clinical syndrome that significantly restricts the chemotherapeutic application of cisplatin in cancer patients. Ferroptosis, a newly characterized programmed cell death driven by the lethal accumulation of lipid peroxidation, is widely reported to be involved in the pathogenesis of cisplatin-associated AKI. Targeted inhibition of ferroptosis holds great promise for developing novel therapeutics to alleviate AKI. Unfortunately, current ferroptosis inhibitors possess low bioavailability or perform non-specific accumulation in the body, making them inefficient in alleviating cisplatin-associated AKI or inadvertently reducing the anti-tumor efficacy of cisplatin, thus not suitable for clinical application. In this study, a novel selenium nanomaterial, polyacrylic acid-coated selenium-doped carbon dots (SeCD), is rationally developed. SeCD exhibits high biocompatibility and specifically accumulates in the kidney. Administration of SeCD effectively scavenges broad-spectrum reactive oxygen species and significantly facilitates GPX4 expression by releasing selenium, resulting in strong mitigation of ferroptosis in renal tubular epithelial cells and substantial alleviation of cisplatin-associated AKI, without compromising the chemotherapeutic efficacy of cisplatin. This study highlights a novel and promising therapeutic approach for the clinical prevention of AKI in cancer patients undergoing cisplatin chemotherapy.© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.