Epithelial cells function as a mechanical barrier against invasion by pathogenic organisms and promote intercellular communication through cell-cell junction complexes. Therefore, the permeability and homeostasis of the gingival epithelial cell layer indicates a defensive capability against invasion by periodontal pathogens. Irsogladine maleate is a medication for gastric ulcer, and is also known to enhance gap junctional intercellular communication in cultured rabbit gastric epithelial and pancreatic cancer cells. We review the effects of Irsogladine maleate on barrier functions and gap junction intercellular communication of gingival epithelial cells under inflammatory conditions, to investigate the prevention of periodontal disease.