Natural stones interact with the environment and undergo several chemical and physical weathering processes that cause the progressive loss of cohesion and degradation/disintegration of the material in the longer term. So, in order to retain the integrity of the historical patrimony and its undeniable impact on society, innovative materials and methodologies have been used in stone conservation field in recent years, also using a more environmentally-friendly approach. In this study, the interaction of three inorganic silica-based consolidant compounds with a valuable artistic calcareous rock, Vicenza stone, is discussed. This specific lithotype results to be still scarcely investigated, despite its high historical relevance and intrinsic features, especially porosity, which make it extensively susceptible to degradation. In particular, a colloidal suspension of silica made by particles with an average diameter of 10–20 nm, and two alkaline silicate solutions (lithium silicate and sodium silicate) are evaluated. An extensive characterization of both treated and untreated Vicenza stone samples was achieved by means of chemical–physical and morphological investigations (water absorption, open porosity, capillary absorption, ultrasonic pulse velocity and static contact angle measurements, Hg intrusion porosimetry, color evaluation, FTIR spectroscopy and SEM analyses). FTIR analyses revealed that all the consolidants exhibited a moderate penetration within the substrate, anyway a significant surface interaction with the stone, especially in the case of alkaline silicates, is proved by the results of SEM analyses, capillary absorption, static contact angle and color change. The improvement of the surface properties after treatments represents an essential and preliminary assumption to enhance the durability performance of Vicenza stone.