The intestine is a hollow tract that primarily transports and digests food. It often encounters mechanical forces and exotic threats, resulting in increased intestinal inflammation attributed to the consistent threat of foreign pathogens. Piezo1, a mechanosensitive ion channel, is distributed broadly and abundantly in the intestinal tissue. It transduces mechanical signals into electrochemical signals and participates in many critical life activities, such as proliferation, differentiation, cell apoptosis, immune cell activation, and migration. Its effect on inflammation has been discussed in detail in systems, such as musculoskeletal (osteoarthritis) and cardiac (myocarditis), but the effects on intestinal inflammation remain unelucidated. Piezo1 regulates mucosal layer and epithelial barrier homeostasis during the complex intestinal handling of foreign antigens and tissue trauma. It initiates and spreads immune responses and causes distant effects of inflammation in the vascular and lymphatic systems, but reports of the effects of Piezo1 in intestinal inflammation are scarce. Therefore, this study aimed to discuss the role of Piezo1 in intestinal inflammation and explore novel therapeutic targets.