Water-based fluids for drilling wells are an environmentally friendly alternative to oil-based formulations typically used in the oil industry. Aqueous mixtures of nonionic monoglyceride surfactants (C6, C8, C10, C12, and C18 carbon chains) and xanthan gum (XG) were investigated with that purpose, correlating their lubricity and solubility in water, as well as using surface tension and contact angle measurements. The results showed that monoglycerides behave as excellent lubricants in water, with a steady decrease of the friction coefficient as the hydrocarbon chain length increased. Monoglycerides were able to reduce the friction coefficient even further when used in XG suspensions, suggesting that they are probably forming a complex with the polysaccharide that shows a synergy toward their performance as lubricants. Experiments of adsorption onto iron oxide nanoparticles also produced evidence of the interaction between these molecules, which favors their adsorption on the metal surface. These results indicate that interactions occurring in solution between the surfactants and the polysaccharide are crucial in the mechanism of action of these mixtures as lubricants in water-based drilling fluids.