This study attempted to scrutinize the potential efficacy of zinc oxide nanoparticles (ZnONPs) and the standard oral hypoglycemic drug glibenclamide in streptozotocin (STZ) -nicotinamide induced diabetic rats. Forty male Wistar rats were divided into four equal groups. Group 1 rats received saline orally and considered as a control group. Other groups were experimentally exposed to diabetes via intraperitoneal injection of STZ and group 2 was left as diabetic non-treated. Group 3 was orally administrated with ZnONPs at a low dose (1mg/kg), and group 4 orally received glibenclamide (600 μg/kg) for 30 days (duration of the experiment). Blood glucose, insulin levels, lipogram profile and pancreatic antioxidant status were improved following ZnONPs or glibenclamide administration as compared to the diabetic group. Moreover, histopathological examination revealed a better outcome in the ZnONPs and glibenclamide treated groups. Although oral treatment of ZnONPs at a low dose 1mg/kg body weight for 30 consecutive days had antidiabetic effect, this effect was less superior to glibenclamide. Therefore, further studies regarding increasing the dose of ZnONPs would be encouraging to get better anti diabetic effect.