The effect of Colatropis gigantea leaf extract was studied on alloxan-induced hyperglycaemic rabbits to evaluate the possible hypoglycaemic and antioxidant properties of Colatropis gigantea (C. gigantean) in diabetes mellitus. Significant decrease (p < 0.05) in the thiobarbituric acid reactive substance (TBARS) was observed in diabetic rabbits administered with the acetone fraction of Colatropis gigantea (C. gigantean) leaf when compared to diabetic control group. Consistent significant increases (p < 0.05) were noticed in the activities of erythrocyte antioxidant enzymes; catalase, superoxide dismutase, and glutathione peroxidase in diabetic rabbits treated with acetone fraction of C. gigantea leaf compared with diabetic control group, although higher activities of these enzymes were observed in diabetic rabbits treated with glibenclamide (reference drug) when compared to the group administered C. gigantea extract. It was also observed that C. gigantea extract had significant increase in vitamin C and protein concentrations when compared with untreated group. These results suggest that acetone extract of C. gigantea leaves possess hypoglycaemic and antioxidant properties.