The nephrotoxicity mechanisms caused by cisplatin (CP), which is used in the treatment of different types of cancer, include several processes, such as DNA damage, apoptosis, inflammation, and oxidative stress. This study investigated the protective effects of Rhododendron luteum leaf extract (RLE) in a rat model of CP-induced nephrotoxicity. Dimethyl sulfoxide extract of RLE was prepared, and its contents were clarified using liquid chromatography-mass spectrometry (LC-MS-MS). Thirty female Wistar Albino rats were divided into five different groups and sacrificed on the seventh day. Biochemical and histopathological analyses were then performed. The presence of quercitrin, quinic acid, chlorogenic acid, protocatechic acid, isoquercitrin, and quercetin was detected in the RLE. While CP significantly increased the levels of oxidative stress, inflammation, and apoptosis markers in the rat kidney tissue and blood samples, treatment with RLE significantly reversed the levels of these parameters in a dose-dependent manner. Total antioxidant status (TAS) values and glutathione (GSH) levels increased significantly in the serum samples from the treatment group compared to the CP group, while blood urea nitrogen (BUN), creatinine, oxidative stress index (OSI), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA) and total oxidant status (TOS) values decreased significantly. GSH levels increased significantly in the treatment group compared to the CP group, while TNF-α, caspase-3 (Casp-3), 8-hydroxy-2'-deoxyguanosine (8-OHdG), OSI, TOS, MDA levels, and damage scores decreased significantly at histopathological examination. In conclusion, RLE exhibited strong protective effects against nephrotoxicity and oxidative damage caused by CP in rats.