The antidiabetic, hypoglycemic and oral glucose tolerance test (OGTT) activities of zinc oxide nanoparticles (ZnONPs) were assessed in mice. ZnONPs were prepared by reacting Zn(NO3)2.6H2O and NaOH solution at 70°C with continuous stirring and then characterized by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) techniques. Diabetes was induced by the intraperitoneal injection of streptozotocin (STZ) in mice, and then the blood glucose levels were determined by the glucose oxidase method. The experimental results revealed that ZnONPs suggestively (p<0.001) declined the blood glucose levels (39.79%), while these reductions were 38.78% for the cotreatment of ZnONPs and insulin, and 48.60% for insulin, respectively. In the hypoglycemic study, ZnONPs (8 and 14 mg/kg b.w) reduced approximately 25.13 and 29.15% of blood glucose levels, respectively. A similar reduction was found in the OGTT test, which is also a dose- and time-dependent manner. Overall, ZnONPs possess a potential antidiabetic activity, which could be validated by further mechanistic studies.