This study was conducted to determine the anti-diabetic effect and safety profile of alkaloids of Acanthus montanus Leaf (AAML). The anti-diabetic study was carried out using alloxan-induced diabetic rats by daily intraperitoneal administration of AAML at doses of 100, 200 and 400 mg/kg for 4 weeks and 8 weeks. The toxicological assessment of AAML was also done by determining the haematological, biochemical and urinary parameters in blood, serum, and urine samples respectively at the end of the tested periods. In the acute toxicity test, mice were administered intraperitoneally with AAML up to 5000 mg/kg. Animals were then observed for behavioural changes; signs of toxicity, and mortality within 24 h. Surviving mice were monitored for 7 days for signs of delayed toxicity. Result of the anti-diabetic study shows significant (P < 0.05) dose-dependent reduction (42.68 %) in blood sugar levels of the hyperglycemic rats when compared with glibenclamide (standard drug). In the acute toxicity test, AAML was practically non-toxic showing no mortality and visible signs of delayed toxicity. The AAML at 4 and 8 weeks elicited significant (P < 0.05) increases in haematological parameters (Hb, PCV, RBC, WBC and differential count), reductions in biochemical parameters (levels of liver enzymes - AST, ALT, and ALP), total cholesterol, triglycerides, urea and creatinine and urinary parameter (pH). Results obtained in this study suggest that the alkaloids of leaf Acanthus montanus leaf is safe when administered intraperitoneally with potential beneficial effects as immunostimulant, hepatoprotective, and hypocholestrolemic agent, when administered over a long period of time.