Interstitial cells of Cajal (ICCs) are pacemaker cells that control smooth muscle contraction in the gastrointestinal (GI) tract. The present study investigated the effects of (SM) on the pacemaker potentials of ICCs from the mouse small intestine and on GI motility . The whole‑cell patch‑clamp configuration was used to record pacemaker potential in ICCs , and GI motility was investigated by recording intestinal transit rate (ITR). Using the whole‑cell patch‑clamp configuration, SM depolarized the pacemaker potentials of ICCs in a dose‑dependent manner. Fulvestrant blocked SM‑induced effects but 1,3‑dihydro‑3,3‑bis(4‑hydroxyphenyl)-7-methyl‑2H‑indol‑2‑one did not. Additionally, 4‑[2‑phenyl-5,7‑bis(trifluoromethyl) pyrazolo[1,5‑a]pyrimidin‑3‑yl] phenol blocked SM‑induced effects. Intracellular guanosine 5'‑O‑(2‑thiodiphosphate), and pretreatment with extracellular Ca‑ and Na‑free solutions also blocked SM‑induced effects. Furthermore, ITR values were increased by SM and SM elevated the levels of motilin (MTL). The SM‑induced increase in ITR was associated with increased protein expression levels of c‑kit and the transmembrane protein 16A (TMEM16A) channel. In addition, SM induced pacemaker potential depolarization through estrogen receptor β in a G protein‑dependent manner via extracellular Ca and Na regulation in the murine small intestine . Moreover, SM increased the ITR through the MTL hormone via c‑kit and TMEM16A‑dependent pathways. Taken together, these results suggested that SM may have the ability to control GI motility and could be used as a GI motility regulator.