Context: Cyclophosphamide ( CTX) is a common anticancer agent used for the treatment of several malignancies. However, upon treatment, it induces severe toxicity due to its oxidative stress capability. Propolis, a natural product collected by honey bees, has shown several biological activities, such as free radical scavenging and antioxidant agent. Objective: This study elucidates the protective effects of propolis against CTX- induced changes in mice. Materials and methods: Forty- eight male Swiss albino mice were divided into four groups; group 1 was intraperitoneally ( i. p.) injected with 200 mL of phosphate buffer saline ( PBS), group 2 was injected with 100 mg/ kg/ d propolis, group 3 was injected with a single dose of CTX ( 200 mg/ kg), and group 4 was injected with a single dose of CTX ( 200 mg/ kg) followed by propolis ( 100 mg/ kg) for 7 consecutive days. After 12 d, mice were bled and then sacrificed to analyze the hematological, biochemical, and histological parameters. Results: The results indicated that CTX- injected mice showed an increase in the levels of alanine aminotransferase ( ALT), aspartate aminotransferase ( AST), urea, and creatinine and a decrease in the total number of white blood cells ( WBCs) and platelets. Moreover, dramatically changes in the histological architectures of the liver and kidney were observed. The mice that were injected with CTX/ propolis showed an improvement in the levels of ALT, AST, urea, creatinine, WBCs, and platelets. Moreover, the histological picture of the liver and kidney was significantly improved. Conclusions: In conclusion, propolis might be considered an effective agent in ameliorating the toxicity resulted from CTX treatment.