Core-shell structures are the most common type of composite material nanostructures due to their multifunctional properties. Silver nanoparticles show broad antimicrobial activity, but the safety of their utilization still remains an issue to tackle. In many applications, the silver core is coated with inorganic shell to reduce the metal toxicity. This article presents the synthesis of various materials based on silver and silica nanoparticles, including SiO2@Ag, Ag@SiO2, and sandwich nanostructures—Ag@SiO2@Ag—and the morphology of these nanomaterials based on transmission electron microscopy (TEM), UV-Vis spectroscopy, and FT-IR spectroscopy. Moreover, we conducted the angle measurements due to the strong relationship between the level of surface wettability and cell adhesion efficiency. The main aim of the study was to determine the cytotoxicity of the obtained materials against two types of human skin cells—keratinocytes (HaCaT) and fibroblasts (HDF). We found that among all the obtained structures, SiO2@Ag and Ag@SiO2 showed the lowest cell toxicity and very high half-maximal inhibitory concentration. Moreover, the measurements of the contact angle showed that Ag@SiO2 nanostructures were different from other materials due to their superhydrophilic nature. The novel approach presented here shows the promise of implementing core-shell type nanomaterials in skin-applied cosmetic or medical products.