Objective: Pyrroloquinoline quinone (PQQ), vitamin C and Syzigium cumini seed extract are known to possess antioxidative properties and can protect diabetes associated oxidative damages. With respect to relative efficacy of PQQ, its comparative effects in regulating diabetes mellitus, practically nothing has been studied so far. In the present investigation we compared the ameliorating effects of PQQ with vitamin C and S.cumini seed extract in STZ-induced diabetes mellitus with an emphasis on the oxidative stress in different organs of mice. Methods: Mice were randomly divided into five groups. Group I receiving only citrate buffer served as the normal control. Animals of groups II-V were rendered diabetic by single dose of streptozotocin (STZ, 150 mg/kg body weight), following which PQQ at a dose of 20 mg/kg, was injected to the animals of group III, while in group IV 50 mg/kg of vitamin C was injected and in group V animals S.cumini seed extract was administered orally 100 mg/kg for 15 days. At the end, alterations in serum different indices including glucose, different lipids, urea, SGPT and SGOT; different tissue antioxidants and histopathological alterations in liver, kidney and pancreas were evaluated. Results: STZ-treated animals developed oxidative stress as indicated by a significant increase in tissue lipid peroxidation, serum glucose, total cholesterol, triglyceride and urea, with a parallel decrease in the levels of tissue antioxidants. When diabetic animals received dose of PQQ, vitamin C and S.cumini in animals of group III, IV and V respectively, these adverse effects were ameliorated. On comparing the ameliorating effects, PQQ appeared to be more effective than vitamin C and S.cumini seed extracts to mitigate diabetes mellitus and its associated oxidative damages. Conclusion: These findings revealed for the first time that, PQQ exhibited better ameliorating potential as compared to vitamin C and S.cumini seed extract.