Transient Receptor Potential Vanilloid (TRPV) channels represent one of the seven subfamilies of TRP receptors and are widely expressed throughout the human body where they play pivotal roles in various physiological processes. In the gastrointestinal (GI) system, TRPV channels regulate critical functions such as nutrient absorption, motility, and secretions. Beyond maintaining physiological equilibrium, these channels are involved in pain and inflammation, contributing to diverse pathologies. Their central role in the pathophysiology of different digestive system disorders has made TRPV channels a significant focus of research. Moreover, the involvement of TRPV channels in numerous GI cancers has further heightened research interest in the role of these channels. Accordingly, this review elucidates the structural components and intricate signaling pathways of TRPV channels, focusing on the unique characteristics of each family member (TRPV1-6) in GI physiology. Furthermore, we explore the therapeutic potential of targeting these channels to modulate their physiological and pathological roles, highlighting their promise in treating GI disorders. Additionally, we address the challenges associated with their therapeutic application, considering their interactions in different systems, inherent biochemical characteristics, and the alterations required for effective design.