Cyclophosphamide (CTX) is used for the treatment of tumors however, it has several side effects which led to failure of the liver functions and significant reduction in the white blood cells total number (W.B.Cs). Spirulina platensis extract (S. platensis) has been found to restore the count of W.B.Cs to normal level with antioxidant properties. The aim of this study is to determine the prophylactic effect of Spirulina extract on CTX-induced hematological, liver and kidney toxicities. Thirty-two male albino mice were divided into four groups (8 mice/group). The first group (G1) was served as a control, the second group (G2) had injected i.p with 200 mg /kg CTX and the third group (G3) had orally treated with S. platensis extract (1000 mg /kg b.w.) for two weeks every day. Group four (G4) had treated orally with 1000 mg/kg of S. platensis extract, and then injected with 200 mg /kg CTX once. Three days after CTX injection, mice were sacrificed and blood samples were collected for complete blood count analysis and biochemical liver and kidney parameters. Liver and kidney tissues were harvested for histological examinations. The results showed that the injection of CTX reduced the total W.B.Cs number and did not affect the red blood cells and hemoglobin or hematocrit levels. Treatment with 1000 mg/kg S. platensis prior CTX treatment for two weeks did not lead to a restoration of W.B.Cs. However, the pre-treatment with S. platensis (1000 mg/kg/body weight) ameliorated the hepatic and renal dysfunctions and decreases the hepatic and renal histological changes which induced by CTX. In summary, the treatment with S.  platensis for two weeks before CTX-injection led to a significant protection on both of the liver and kidney organs in mice.