Introduction: Portulaca oleracea (PO) plant, Omega 3, and Sodium Selenite plus Vitamin E have antidiabetic effects by compensating for the deficiency in insulin release and enhancing antioxidant status. The purpose of the present study was to comparatively assess the effect of Portulaca oleracea, omega-3, and a combination of Sodium Selenite and Vitamin E on hepatic enzyme activities in streptozotocin-induced diabetic Rats. Materials and methods: A total of 48 adult male Wistar rats (weighing approximately 220 ± 10 g) were injected by a single intraperitoneal injection of streptozotocin (60 mg/kg body weight.) and were randomly assigned to 4 groups, and 4 replicates for each group. Group 1 served as diabetic control, groups 2, 3, and 4 received Portulaca oleracea extract (1.5 mg/kg/day, orally), Omega-3 (500 mg/kg/day, orally), and Sodium Selenite (0.5 mg/kg/day, orally) plus Vitamin E (400 Iu/kg/day, orally), respectively, for 28 days. At the end of the study, blood samples were taken for biochemical investigations. Results: The levels of blood glucose, AST, ALP, and GGT enzymes in all treatment groups were less than those of the control group. The ALT enzyme activity in rats treated with Portulaca oleracea and Vitamin E plus Selenium was less than in control and omega-3 treatment groups. Conclusion: Results indicated that Portulaca oleracea is more effective in hepatic enzyme activities of diabetic rats, compared to other treatment groups.