Zinc oxide nanoparticles (ZnO NPs) have a wide range of applications, and their properties can be significantly affected by gamma (gamma) radiation, particularly in metal oxide semiconductor-based devices. This study investigates the impact of gamma-irradiation on the physicochemical properties of ZnO NPs. The ZnO NPs were synthesized using a microwave method with zinc nitrate hexahydrate as a precursor and urea as a fuel. These synthesized ZnO NPs were exposed with gamma rays emitted from 60Co radioactive source at different doses (0, 25, 50, and 75 kGy). We systematically examined the effects of gamma irradiation on the structure, optical properties, and colloidal stability of the ZnO NPs using various techniques, including XRD, Raman spectroscopy, FTIR, SEM, UV-visible absorption, and zeta potential/particle size analysis (ZP/PSA). The characterization results revealed that gamma irradiation caused significant alterations in the microstructure of ZnO NPs, resulting in reduced crystallite and grain sizes. Additionally, the optical properties and colloidal stability were found to be dose-dependent, with absorption spectra shifting towards the blue region, an increase in optical bandgap, and a decrease in zeta potential values as the dose rate of gamma radiation increased.