Studying the effect of radiation on the stability and properties of nanoparticles is an important step in the development of drug delivery systems and radiopharmaceuticals. This work investigates the effect of gamma radiation with a total dose from 3 to 127 kGy on aqueous dispersions of poly(lactide-co-glycolic acid) (PLGA) nanoparticles stabilized with polyvinyl alcohol (PVA). It is found that after irradiation with doses up to 20 kGy, destruction occurs rapidly, and then it slows down. At the same time, the glass transition temperature of the PLGA core is practically unchanged and remains in the range of 37–38°C. The hydrodynamic diameter of the particles decreases due to the destruction of the PVA polymer chains. The hydrolysis of the irradiated and non-irradiated particles occurs at similar rates, which is probably explained by the glassy state of the core.