The interstitial cells of Cajal (ICCs) play an important role in maintaining the normal function of gastrointestinal dynamics. In our previous study, we reported that, in advanced gastric cancer, the frequency of bowel movement is always reduced, due in part to the decreased number of ICCs. To investigate the impact of ICCs in gastric cancer, we established a mouse model of gastric cancer peritoneal metastasis using SGC-7901 gastric adenocarcinoma cells and their supernatant. Then, stem cell factor (SCF) and ouabain were used as therapeutic agents to improve gut dynamics. Our data showed that, compared with the normal mice, treatment with SGC-7901 cells and their supernatant led to a significant reduction of the muscle layer thickness, a decreased number of ICCs, broadened gaps between ICCs and surrounding cells, degeneration and necrosis of smooth muscle cells (SMCs), and infiltration of inflammatory cells. In contrast to SGC-7901 cell and supernatant treatment, SCF intervention caused mild submucosal edema and mitochondrial proliferation in the ICCs and SMCs. Additionally, ouabain treatment led to inflammatory cells infiltration into the submucosa and a decreased volume of ICCs. In conclusion, our data illustrated that, under the condition of gastric cancer peritoneal metastasis, the dysfunction of intestinal peristalsis may be related to pathological changes in ICCs. Moreover, we demonstrated that SCF treatment may help to improve intestinal dynamics by regulating the number and function of ICCs.