Cisplatin is an effective chemotherapeutic drug widely used for the treatment of various solid tumors; however, its clinical use and efficacy are limited by its inherent nephrotoxicity. The pathogenesis of cisplatin-induced nephrotoxicity is complex and has not been fully elucidated. Cellular uptake and transport, DNA damage, apoptosis, oxidative stress, inflammatory response, and autophagy are involved in the development of cisplatin-induced nephrotoxicity. Currently, despite some deficiencies, hydration regimens remain the major protective measures against cisplatin-induced nephrotoxicity. Therefore, effective drugs must be explored and developed to prevent and treat cisplatin-induced kidney injury. In recent years, many natural compounds with high efficiency and low toxicity have been identified for the treatment of cisplatin-induced nephrotoxicity, including quercetin, saikosaponin D, berberine, resveratrol, and curcumin. These natural agents have multiple targets, multiple effects, and low drug resistance; therefore, they can be safely used as a supplementary regimen or combination therapy for cisplatin-induced nephrotoxicity. This review aimed to comprehensively describe the molecular mechanisms underlying cisplatin-induced nephrotoxicity and summarize natural kidney-protecting compounds to provide new ideas for the development of better therapeutic agents.