During radiotherapy, ionizing irradiation interacts with biological systems to produce free radicals, which attack various cellular components. The hematopoietic system is easily recognized to be radiosensitive and its damage may be severe. Melanin nanoparticles (MNPs) act as free radical scavengers prepared by polymerization of dopamine. In this study, a total of 110 male BALB/C mice were divided into five equal groups. Each group contained 22 mice. Mice of group A did not receive MNPs or irradiation (control group), group B was injected intraperitoneally (i.p.) with 50 mg/kg MNPs. Mice of group C and D were exposed to a dose of 7 Gy ɣ-irradiation and injected with the same dose of MNPs as in group B either 30 min pre- or post-irradiation, and group E was exposed to a dose of 7 Gy ɣ-irradiation only. The impact of MNPs on peripheral blood, spleen, and DNA damage induced by irradiation was evaluated by blood count, histopathology of the spleen, and comet assay for the DNA in the bone marrow at 1, 4, 8, and 12 days post-irradiation. Results of group E compared with control group (A) showed a significant depression in complete blood count. Additionally, histopathological observation showed the absence of megakaryocytes with delayed time post-irradiation, deposition of eosinophilic protein of their spleen appeared, as well as a remarkable decrease in spleen size was observed. Moreover, ɣ-irradiation-induced DNA damage as can be inferred from a significant increase by about 5-10 folds in all comet parameters (% of DNA, tail length, tail moment, and olive moment) in the DNA of the bone marrow. In contrast, pre-post treatment with MNPs protected hematopoietic tissues against radiation damage, and therefore, enhanced the survival of mice with 40 % in groups (C&D) compared with 10 % to group (E) till 30 days post-irradiation. In conclusion, these results demonstrated that synthetic MNPs provide significant radioprotection to the hematopoietic tissues.