Cisplatin and other chemotherapy agents are critical for cancer treatment but pose a significant ecotoxicological risk following excretion into the environment. This study examined the efficacy of Cucurbita maxima (pumpkin) seed extract, a natural antioxidant source, in alleviating cisplatin-induced nephrotoxicity in an albino rat model. Forty rats were divided into four groups: a negative control, a positive control (cisplatin only), and two treatment groups receiving cisplatin alongside pumpkin seed extract at 300 mg/kg or 600 mg/kg body weight. Nephrotoxicity was assessed via serum biomarkers (urea, creatinine, total protein, albumin, and electrolytes) and histopathological examination. Phytochemical analysis verified the existence of flavonoids, phenolic compounds, and additional antioxidants, with the extract exhibiting a significant (92%) DPPH radical scavenging activity. Cisplatin administration significantly (p<0.05) elevated urea and creatinine levels and induced severe tubular necrosis and leukocytic infiltration. Co-treatment with the pumpkin seed extract, particularly at 600 mg/kg, markedly attenuated these effects, significantly restoring renal function markers and preserving histological architecture. The findings demonstrate that Cucurbita maxima seed extract possesses significant renoprotective properties, primarily attributed to its potent antioxidant constituents. This research highlights the value of plant-derived bioactive compounds as potential natural adjuvants to reduce the toxic side effects of pharmaceutical contaminants, offering insights relevant to both biomedical science and environmental toxicology.