The ameliorative effects of Opuntia vulgaris fruit extract (OE) were evaluated against methanol-induced haematological and biochemical toxicity in rats. The methanol-induced haematological and biochemical perturbation significantly decreased the levels of red blood cell (RBC), haemoglobin (Hb), haematocrit (Ht), serum total protein and increased glucose, cholesterol, and triglyceride levels in serum. Treatment of rats with methanol significantly increased lipid peroxidation (LPO) level and decreased the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in erythrocytes. OE treatment could increase significantly the levels of RBC, Hb, Ht and total protein, and decrease glucose, cholesterol and triglyceride levels in serum, and increase the activities of SOD, CAT and GPx in erythrocytes, when compared with methanol-treated group. Spleen histopathology showed that OE could significantly reduce the incidence of spleen lesion induced by methanol. These results suggested that OE could exhibit a potential source of natural antioxidants against methanol-induced haematological and biochemical disruption in rats. The protective effects of OE may be due to the modulation of antioxidant enzymes activities and inhibition of LPO.