Nephro-and hepatotoxicities are important complications in cancer patients undergoing cisplatin (CP) therapy. We aimed to study the protective effect of fenugreek (FG) on CP induced renal and hepatic injuries in rats. Cisplatin intoxication resulted in structural and functional renal and hepatic impairments, which were revealed by massive histopathological changes and elevated kidney and liver function tests. However, it was associated with oxidative stress and lipid peroxidation as evident by increased reactive oxygen species (ROS) and malondialdehyde (MDA) with decreased levels of total antioxidant activity. Cisplatin administration triggered inﬂammatory responses and apoptosis in rat livers and kidneys as evident by increased expression of pro-inﬂammatory cytokine, tumor necrosis factor- α (TNF-α) and apoptotic marker p38 mitogen-activated protein kinase (p38 MAPK) as results of overproduction of ROS. FG signiﬁcantly attenuated the cisplatin-induced biochemical and histopathological alterations, inﬂammation and apoptosis in rat livers and kidneys. Results suggested that fenugreek co-administration has a powerful antioxidant effect and may serves as a novel and promising preventive strategy against cisplatin-induced nephron- and hepatotoxicities.