In this work experimental and theoretical evaluations of the wettability alteration of sandstones, using the commercial surfactant polysorbate 80 (P80), are presented. The experimental evaluation started from a virgin sandstone core (water-wet); damage was then induced to modify the wettability of the rock from water-wet to oil-wet, with the purpose of evaluating the surfactant's ability to restore the wettability of the core to the water phase. The contact angles of water and ndecane droplets were used to evaluate the wettability alteration of the surface. The theoretical evaluation was made using molecular dynamics to determine the configuration of the surfactant adsorbed on the surface and to calculate the surfactant liquid interaction energy. Experimental results showed that a concentration of 100 ppm P80 in the impregnation solution generated the greatest contact angle for n-decane droplets and a small contact angle for water droplets using the least amount of surfactant, restoring the water-wet state of the solid and generating a lipophobic surface. The molecular dynamics results showed that adsorption of the surfactant on the surface is associated mainly with interactions between the chains of the surfactant that contain the ester group and the surface, whereas the chains containing ethylene oxides are exposed toward the liquid phase. By evaluating the interaction energy between the P80 coating and the liquid phases, it was established that the chains containing the ethylene oxides were key to restoring the water-wet state of the surface since they exerted an attractive interaction over water and a slightly repulsive interaction over n-decane, generating the lipophobic surface. The molecular model developed in this work allows the performance of predictive calculations of the contact angle of liquid droplets, with deviations, in most cases, of less than 5% compared to the experimental value.