Background: A major side effect of cyclophosphamide (CPA) during chemotherapy is hemotoxicity. Use of natural products like royal jelly reduced the adverse effect of a drug. A current study was an effort to find out the potential defensive effects of royal jelly against hemotoxicity induced by cyclophosphamide in male albino mice. Methods: Male Swiss albino mice of 20±5 gms were unevenly divided into six groups; G1: normal control group 0.9% saline solution I.P. weekly, G2: royal jelly (100 mg/kg/d) CMC suspended administered by orally, G3: cyclophosphamide (50 mg/kg/week) was injected intra-peritoneally, G4: I.P. cyclophosphamide (50 mg/kg/week) along with royal jelly (100 mg/kg/d), G5: I.P. cyclophosphamide (50 mg/kg/week) with royal jelly (250 mg/kg/d), G6: I.P. cyclophosphamide (50 mg/kg/week) and royal jelly (500 mg/kg/d). The experiment lasted for 12 weeks. The measurement of hematological parameters CBC was performed using automated hematology system. Mean±SEM one way ANOVA followed by Tukey's test were performed to find out the significant difference between groups. Results: Cyclophosphamide treated mice exhibit leucopenia, erythrocytopenia, thrombocytopenia and the significant reduction in hemoglobin (Hb), packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) as compared to control group. The administration of royal jelly to CPA treated mice, according to the present experimental plan significantly improves the alterations induced in haemogram. Conclusion: It was suggested that royal jelly ameliorate cyclophosphamide-induced hematological alterations, thus it might be used as a dietary protective natural remedy during the chemotherapy.