NSAIDs are widely used in clinical practice, but frequently cause upper gastrointestinal injury, posing an important challenge. These injuries are primarily caused by prostaglandin deficiency and a topical effect, leading to ulcers or bleeding with few symptoms. The increasing number of elderly patients and those receiving antithrombotic therapy further complicates and exacerbates NSAID/low-dose aspirin–induced injury. For the upper gastrointestinal tract, the efficacy of PPIs/PCABs and H. pylori eradication is well established. The Japanese evidence-based clinical practice guidelines for peptic ulcer disease, revised in 2026, will incorporate updated evidence and provide clearer direction for standard management. In contrast, effective therapies and management strategies for NSAID-induced small-bowel injury remain undefined, highlighting the need for new pathophysiological insights and therapeutic approaches. This symposium aims to summarize recent findings on the epidemiology, pathophysiology, treatment, and prevention of NSAID-induced gastrointestinal injury and to discuss future perspectives for the comprehensive management of the entire gastrointestinal tract.