The interaction of microorganisms with stone materials leads to biodeterioration processes, which may cause aesthetic damages and the loss of durability and strength of the substrates. Innovative solutions against this process are represented by nanotechnologies. In our previous works, 2-mercaptobenzothiazole was successfully encapsulated within two silica-based nanodevices: nanocapsules and mesoporous nanoparticles. Such loaded nanodevices have been dispersed in TEOS based coatings, characterized as far as their chemical–physical properties and in vitro biocide efficacy. Here, we adopt a multi-technic approach, to assess the coatings efficacy and compatibility with four types of stones of cultural heritage interest, namely, mortar, brick, travertine, and Carrara marble. In particular, we determine the protective function of the coatings, based on water transport properties (reduction up to a factor 10 of the water absorption for brick and mortar, without significantly influencing water vapor transmission rate), morphology of the surface (absence of coating cracks and color changes), and TiO2 photocatalytic activity. Consequently, these coatings can be considered suitable for application on stone artifacts, without interfering with their artistic appearance.