Gastroesophageal reflux disease (GERD) is a common digestive disorder characterized by the reflux of gastric contents into the esophagus, leading to mucosal damage and inflammation. Claudin proteins play a crucial role in forming intercellular tight junctions, maintaining the barrier function between epithelial cells, and actively participating in defense mechanisms against reflux. Claudin proteins hold potential as biomarkers for the diagnosis and treatment of GERD, offering a new perspective for understanding the pathogenesis of the disease. This article reviews the changes in the expression of claudin proteins in GERD patients and their potential mechanistic roles in the esophageal mucosal barrier.