The intestines are in a constant state of motion and self-renewal. The mechanical breakdown of food facilitates intestinal movement and aids digestion. It is believed that mechanical stimulation, triggered by changes in osmotic pressure within the intestines, plays a crucial role in regulating gastrointestinal motility. While TRPs and PIEZO1/2 have been identified as mechanosensitive ion channels involved in this process, there still exist numerous unidentified channels with similar properties. In this study, we demonstrate that the TMEM63B expressed in intestinal stem cells contributes to the regulation of intestinal motility and digestion. The deletion of TMEM63B in intestinal stem cells not only decelerates intestinal motility and impairs digestion but also attenuates the proliferation of intestinal stem cells and exacerbates DSS-induced colitis in mice. Collectively, our findings unveil the pivotal role of TMEM63B in governing optimal digestive function and modulating intestinal motility