Alkaline earth metal oxides (MO) are catalytically active in the etherification of glycerol. Density Functional Theory (DFT) calculations have been used to examine the reactivity of glycerol with MO surfaces with M=Mg, Ca, Sr or Ba. More specifically, the optimum glycerol adsorption mode and the strength of glycerol interaction with regular MO (001) surfaces and a stepped CaO surface have been investigated and involves the interaction with acid-base surface sites. The basicity of lattice oxygen atoms is correlated with the adsorption energy: BaO (-3.02 eV) > SrO (-2.85 eV) > CaO (-2.05 eV) > MgO (-1.35 eV). The interactions have an exothermic character, that is, the more basic the alkaline earth metal oxide, the more exothermic is the adsorption process and the higher the dissociation extent. Thus, the dissociation of glycerol increases in the order: MgO (not dissociated) < CaO (partially dissociated < SrO (partially dissociated) < BaO (completely dissociated). The presence of defects is found to play a key role in the mechanism: glycerol interaction with a stepped CaO surface presents the highest adsorption energy (-3.78 eV), and the molecule is found to dissociate at the step. The calculated structural parameters are found to be in good agreement with experimental data on catalyst reactivity. Moreover, the earlier postulated reaction mechanism, which also involves the additional involvement of Lewis acid sites proved to be feasible for CaO and SrO regular surfaces, and for the stepped CaO surface. It was found that for these oxides one of the most favored adsorption modes involves a non-dissociative adsorption of one hydroxyl group of glycerol, which as a result becomes a better leaving group. Therefore, theoretical evidence was found for the possible direct involvement of Lewis acid sites in the catalytic etherification of bio-derived alcohols, such as glycerol, as it is anticipated that these observations can be extended to sugar alcohols as well.