Background: Toxicity due to drugs used for neoplastic disorders is documented in previous studies. Cyclophosphamide (CP) is a widely used as anticancer drug, which could cause toxicity of normal cells through its toxic metabolites. The fullerene family, especially Fullerene C₆₀ nanoparticles (NPs) can be utilized in many and different biological fields. We evaluated the protective role of Fullerene C₆₀ (NPs) in the toxicity induced by cyclophosphamide. Methods: The activities of serum Liver marker enzymes; alanin amino transferase (ALT) and aspartate amino transeferase (AST), alkaline phosphatase (ALP). T. protein, Albumin, serum heart marker enzymes; Lactate dehydrogenase (LDH) and creatinine phosphokinase (CK) were determined. Results: Toxicity of the organs like heart, and liver was proved from increases of ALT, AST, ALP, LDH and CK values and a decrease in T. protein and Albumin in cyclophosphamide (200 mg/kg a single dose) administered rats, Fullerene C₆₀NPsdissolved in olive oil (0.8 mg/ml) oral treatment will show enhancement against toxicity induced by (CP)at a dose of 4 mg/kg body weight daily for 10 days. Conclusion: In this study, we wish to report that, the in vivo treatment of Fullerene C₆₀ (NPs) was improved the biochemical changes caused by cyclophosphamide-induced toxicities. These results have importance in the fields of medicine. This may open the way for the biomedical applications of C₆₀in treatment of cancer, neurodegenerative disorders, and ageing.