Zinc Coumarate and zinc caffeiatenano-particles (ZCoNPs, ZCaNPs) have been shown to affectthe different biological processes. This work was undertaken to evaluate the mitigating action of ZCoNPs in combination with ZCaNPsagainst liver damage induced by gamma rays (γ-rays). Rats were exposed to 7Gy of γ-rays, and theninjected intraperitoneally (i.p.) with ZCoNPs [2U / rat / day (5 mg/kg)], and ZCaNPs [2U / rat / day (15 mg/kg)] for 7 consecutive days.The results showed that irradiated rats treated with ZCoNPs (5 mg/kg/body weight) in combination with ZCaNPs (15 mg/kg/body weight) for 7 days revealed a significant increase in the body weight, antioxidants levels, T Helper (CD4) Cell and T Cytotoxic (CD8), associated with amarked decrease in the level of lipid peroxidation (LP), nitric oxide(NOx), total free radicals concentrate (TFRC), and DNA fragmentation. Moreover, positive alterations in the morphological state, hematological parameters, and thecell cycle phases were noticed. Additionally, the histopathological study demonstrated an improvement in the liver tissue of irradiated rats after treatment.Thus, ZCoNPs and ZCaNPscould be usedas a natural mitigating agent to reduce the hazards of ionizing radiation.