Background:Croton membranaceus (CM) is used for benign prostate hyperplasia treatment.Objective:Sub-chronic toxicity studies are non-existent and provided the basis for this study.Materials and Methods:90 days oral administration of a low dose (LD) (30 mg/kg b. wt.), medium dose (MD) (150 mg/kg b. wt.), and high dose (HD) (300 mg/kg b. wt.) CM aqueous root extract to 3 groups (n=6 each) of male Sprague-Dawley rats, alongside a control group, was undertaken. Urinalysis, hepato-renal function tests, lipid profile, cardiac enzymes, and routine hematology tests were performed.Results:Triglyceride levels (C=1.05±0.19, LD=0.64±0.08, MD=0.55±0.04, HD=0.50±0.02 mmol/L) were significantly reduced (P<0.05). Very low density lipoprotein (C=0.48±0.09, LD=0.29±0.04, MD=0.25±0.02, HD=0.23±0.01 mmol/L) decreased significantly (P<0.05). Cardiac enzymes-creatinine kinase (C=568±172, LD=315±79, MD=441±209, HD=286±81 IU/L) decreased markedly (P<0.05) alongside lactate dehydrogenase (C=2675±875, LD=1667±1229, MD=1186±442, HD=855±239 IU/L) (P<0.05).Conclusion:C. membranaceus aqueous root extract is non-toxic but demonstrates anti-atherogenic and anti-ischemic potentials.