Because of their unique properties which are strongly dependent on the physicochemical properties of metal nanomaterials, noble metal nanostructures, particularly silver, have attracted much attention in the fields of electronics, chemistry, physics, biology, and medicine. Regarding biology and medical applications, silver nanoparticles (NPs) are recognized as a promising candidate to fight against resistant pathogens because of their significant antimicrobial activities. However, there are two major ignored issues with these NPs. First, the effect of various types of bacteria on antibacterial efficacy of silver NPs is ignored; second, there is no information on the pattern and compositions of both soft- and hard-corona proteins at the surface of NPs, which can define cellular responses to the NPs. In this article, the bacterial effect on the antibacterial capability of silver NPs with various geometries (i.e., sphere, wire, cube, and triangle) was probed; in this case, three different types of bacteria including Escherichia coli (E. coli), Bacillus subtilis, and Staphylococcus aureus were employed. The results showed that the type of bacteria can have quite a significant role in the definition of antibacterial efficacy of NPs, which has significant implications in the high yield design of NPs for antibacterial applications and will require serious consideration in the future. In addition, both soft- and hard-corona proteins were analyzed, and the effects of protein coated NPs on normal cells were evaluated. According to the results, the composition and thickness of protein coronas were strongly dependent on the physicochemical properties of silver NPs. We have found that the composition and thickness of the protein corona can evolve quite significantly as one passes from particle concentrations and shapes appropriate to in vitro cell studies to those present in in vivo studies, which has important implications for in vitro-in vivo extrapolations and will require more consideration in the future.