Prostaglandins play important roles in the gastric mucosal protection and gastric ulcer healing. Administration of the prostaglandin derivatives has been proven to be effective for both treatment and prevention of gastric ulcers associated with non-steroidal anti-inflammatory drugs (NSAIDs). The risk of postoperative hemorrhage following gastric endoscopic submucosal dissection (ESD) is higher in patients with antithrombotic therapy. Mucosal protective agents, including prostaglandin derivatives, may be effective in preventing post-ESD hemorrhage in patients on antithrombotic therapy. Recently, NSAIDs-induced small intestinal damages are recognized by video capsule endoscopy and balloon endoscopy. Prostaglandin derivatives are also useful for these small intestinal damages.