Background: The liver and kidney are organs affected by chemotherapy drugs such as cyclophosphamide (CP). This study examined the protective effects of treatment with saponin (SP) against CP-induced nephrotoxicity and hepatotoxicity. Methods: 24 adult male mice were divided into four groups (N 5 6): Control group, CP (15 mg kg 1), SP (2.5 mg kg 1) and CP t SP. After treatment, blood samples were collected for the determination of biochemical parameters. Liver and kidney samples were taken for histological analysis and assessment of oxidative stress and inflammatory markers. Results: Cyclophosphamide decreased renal and liver functions and antioxidant enzymes, which significantly increased blood urea nitrogen and creatinine (BUN, Cr), liver enzyme levels, malondialdehyde, nuclear factor kappa ƒŔ (NF-kB) and Interleukin 1 beta (IL-1B) concentrations. Moreover, histopathological findings of the CP group showed that there were acute tubular necrosis and glomerular atrophy in the renal tissues and lymphocyte infiltration in the liver samples. Treatment with saponin improved hepatic and renal functions, pathological changes and antioxidant capacity, and also decreased lipid peroxidation and inflammation. Conclusion: It seems that saponin could exert a hepato-nephroprotective effect against cyclophosphamide toxicity.  Kulcsszavak: antioxidants, cyclophosphamide, inflammation, kidney, liver, saponin