<b><i>Introduction:</i></b> Ionizing radiation (IR) causes oxidative stress in kidneys and subsequently disrupts renal function. The use of green synthesized zinc nanoparticles (Zn NPs) with antioxidant properties may reduce the damage caused by IR. <b><i>Methods:</i></b> Thirty-six mice were kept in a standard situation and divided into 6 groups: 1: Control; 2–4: receiving 5 mg/kg, 10 mg/kg, and 25 mg/kg of Zn NPs with IR; 5: receiving 5 mg/kg of ZnSO<sub>4</sub> with IR; and 6: IR. After 15 days, half of the animals in each group were sacrificed and their blood samples isolated to evaluate the plasma urea and creatinine levels. The kidneys were kept for evaluating the glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels; on 21st day, the rest of the animals were sacrificed and their kidneys removed for histological assessments. <b><i>Results:</i></b> IR decreased GSH content, increased MDA level, and reduced SOD and CAT activity. On the other hand, Zn NPs at 10 and 25 mg/kg doses increased GSH, decreased MDA, and enhanced SOD and CAT activities. Zn NPs treatment at 10 and 25 mg/kg doses decreased the plasma urea and creatinine levels induced by IR. Moreover, Zn NPs significantly decreased the level of urea and creatinine in irradiated mice in comparison with IR alone (<i>p</i> < 0.05). The main histopathological results were tubular and glomerular atrophy and interstitial fibrosis in irradiated mice, while tubular degeneration and atrophy were less frequent in Zn NPs + IR group than in IR group alone. <b><i>Conclusion:</i></b> Zn NPs treatment, especially at 25 mg/kg dose, attenuates the side effect of IR on kidneys through reducing oxidative stress factors, biochemical, and histopathological changes.