Background: Diabetes mellitus (DM) is the most common endocrine disorder. There is a strong need for new drugs with little adverse effects. Canagliflozin is approved as SGLT2-inhibitor and Portulaca oleracea, herbaceous plant, have a considered efficacy and safety in glycemic control with little side effects. Objectives: Comparing the effects of Portulaca Oleracea water extract and Canagliflozin (Invokana) on alloxan-induced diabetes in adult male albino rat. Materials and Methods: Eighty albino rats were randomly categorized into 8 equal groups. Group I (normal control) and group II (diabetic control) were gavaged with normal saline. Three normal groups (groups III, IV, V) and three diabetic groups (groups VI, VII, VIII) were treated with Portulaca Oleracea extract (250 mg/kg body weight), Canagliflozin (10 mg/kg body weight) and both Portulaca  Oleracea and Canagliflozin in the same doses respectively. Blood and tissue samples were obtained for analysis after 10 weeks of treatment. Results: More significant reduction occured in serum glucose level by canagliflozin. Elevated liver enzymes, blood urea nitrogen and lipid profile improved more by Portulaca. Portulaca has an antioxidant activity. Conclusion: Portulaca  Oleracea extract is more potent anti-oxidant, tissue protective and regenerative agent for liver and kidney, but weaker hypoglycemic agent than canagliflozin.