The aim of this study was to obtain useful information about the behavior of a coating when it interacts with a stone substrate, to allow the choice of the most suitable protective agent to preserve stone artworks from deterioration phenomena in their environmental conditions. The effect of some commercially available silane-based polymers on Lecce stone was compared with that of two new acrylic ones not yet available for sale. The performance of each protective treatment was evaluated by colorimetry, contact angle measurements and NMR relaxometry, which allows to estimate the hygroscopic properties of the stone in terms of open porosity and water-uptake. The microscopic observations combined with micro-FTIR and SEM-EDS analyses were performed to investigate the distribution of the protectives on the stone surface and their depth of penetration. The results showed that the water repellency of the two acrylic products and of one of the silane-based protectives was mainly due to a surface effect, just slowing down water adsorption. On the contrary, the other two silane-based products turned out distributed throughout most of the sample volume, completely hindering water absorption.