Gastrointestinal (GI) epithelial ion transport is physiologically important in many aspects of humans, such as in maintaining fluid balance of whole body, and also plays a role in the development and progression of common GI disease. Estrogen and estrogen receptors have been shown to modulate the activity of epithelial ion secretion in GI tract. This review aims to address the current state of knowledge about the role of estrogen and estrogen receptors in modulation of GI epithelial secretion and to elucidate the underlying mechanisms. We highlight the recent findings regarding the importance of estrogen and estrogen receptors in GI epithelia protection and body fluid balance by modulation of gastrointestinal epithelial HCO3- and Cl- secretion, especially current information about the regulatory mechanisms of duodenal HCO3- secretion based on our study in this field. Since there are no reviews on this topic but only few papers to address the main issues, we hope to timely provide new perspectives for the association between estrogen and GI disease.