The oral epithelium represents a major interface between an organism and its external environment. Improving this barrier at the molecular level can provide an organism added protection from microbial-based diseases. Barrier function of the Gie-3B11-human-gingival-epithelial-cell-culture model is enhanced by the micronutrients zinc, quercetin, retinoic acid, and acetyl-11-keto-β-boswellic acid, as observed by a concentration-dependent increase in transepithelial electrical resistance and a decrease in transepithelial C-d-mannitol permeability. With this improvement of tight-junction (TJ)-barrier function (reduced leak) comes a pattern of micronutrient-induced changes in TJ claudin abundance that is specific to each individual micronutrient, along with changes in claudin subcellular localization. These micronutrients were effective not only when administered to both cell surfaces simultaneously but also when administered to the apical surface alone, the surface to which the micronutrients would be presented in routine clinical use. The biomedical implications of micronutrient enhancement of the oral-epithelial barrier are discussed.