Given the pivotal role of the tuft cell—IL-25 axis (tuft/IL-25 axis) in initiating innate type 2 responses via ILC2s within the inflammatory milieu of IBD, this review focuses on dissecting the complex immunoregulatory crosstalk mediated by IL-25 and tuft cells in the IBD inflammatory milieu and the multifaceted pathogenesis of IBD. Here, IL25 is linked to inflammatory bowel disease.