This study aimed to investigate ameliorative effects of the crude extract (SIE) and polysaccharide (SIP) of the ink of Sepia officinalis, on some biochemical and hematological disorders induced by cyclophosphamide (CP). Forty adult male albino Wistar rats were divided into five groups (n= 8 each). In the control group, rats were administered orally with 0.9% isotonic saline solution at a dose (5 ml/kg b.w.). All the other groups were i.p. injected with a single dose of CP (200mg/kg b.w.) only for one time. Then the third group was treated with oral administration of (SIE) (200mg/kg b.w.) daily for 60 days, the fourth group was treated with oral administration of (SIP) (80mg/kg b.w.) daily for 60 days and the fifth group was treated with oral administration of (SIE, 200mg/kg b.w. + SIP, 80mg/kg b.w.) daily for 60 days. All the animals were slaughtered by the end of the experiment for collecting the blood samples for hematological and biochemical assays. The biochemical results indicated that administration of CP was associated with a significant increase in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine and uric acid. Moreover, a significant decrease in the levels of albumin and total protein was recorded. In addition, hematological disorders including a significant suppression on the numbers of RBCs, WBCs and PLTs, with a remarkable reduction in hemoglobin contents (Hb) and a significant drop in PCV values. Concomitant administration of SIE and SIP alleviated the altered biochemical and hematological parameters.