Metallic nanoparticles (NPs) made by traditional means have a deleterious effect on bone marrow (BM) cells. Alternatively, green-synthesized NPs are cost-effective, ecofriendly, and may be less toxic. Also, albumin is a biocompatible blood protein involved in several physiological processes, employed in drug delivery without posing adverse effects, and is thought to be ideal NPs or coating for reducing the metallic NP's toxicity. We prepared albumin NPs (AlbNPs), biosynthesized silver NPs (AgNPs) using the metabolite of the Escherichia coli D8 strain and coated them with albumin (Ag/AlbNPs). These NPs were characterized and intraperitoneally administered to rats to compare their effect on rat BM cells. The flow cytometry results revealed that AgNPs significantly reduced viability, increased apoptosis, downregulated the antiapoptotic Bcl2 gene expression, and upregulated the apoptotic genes Bax and p53 in BM cells, while treatment with AlbNPs maintained these parameters. Principally, AgNPs caused significant DNA fragmentation, since all parameters observed by the comet assay (tail length, tail DNA content, tail moment, and olive moment) were significantly higher in AgNP-treated groups than in control and AlbNP-treated groups. Investigation of the cell cycle revealed that treatment with AgNP, but not AlbNPs, downregulated the expression of the regulatory genes Cdk2, Cdk4, and the cyclins A1 (Ccna1) and D1 (Ccnd1), which resulted in the arrest of the progression of the cell cycle at GO/G1, as demonstrated by flow cytometry. Coating AgNPs with albumin increased their size, and decreased their intracellular concentration, resulting in reduced apoptosis and cell cycle arrest. However, these results for the Ag/AlbNP-treated group were still not comparable to those treated with pure AlbNPs. In conclusion, in contrast to AlbNPs, green AgNPs are toxic to bone marrow cells. Their coating with albumin, however, reduces this toxicity. To avoid this metal NP toxicity, it is recommended to use compatible degradable NPs instead of metal NPs for medication delivery to BM.