In this novel research, ZnO–insulin nanoparticles were prepared as glucose level regulator in the blood by sol-gel route adopting micelle template approach. The physicochemical features of the novel nanoparticles were investigated by XRD, FTIR, EDX and HRTEM which reveal noted crystallinity distortion when insulin is present. ZnONPs slight crystallite distortion could aid formulating ZnONPs activity biomedically in presence of protein entities. A homogeneous dispersion of insulin on the surface of ZnONPs was detected by HRTEM could also indicate favorable attachment mutual sites between the ZnO surface and the structural amino acid groups. The hypoglycemic activity effect of ZnONPs, ZnONPs-Insulin (1:1) and ZnONPs-Insulin (1:0.5) drugs was proven and compared to that of insulin in this study. The data showed that ZnONPs-Insulin (1:1) drug was the most potent hypoglycemic agent of them.