Neurointestinal diseases result from dysregulated interactions between the nervous system and the gastrointestinal (GI) tract, leading to conditions such as Hirschsprung's disease and irritable bowel syndrome. These disorders affect many people, significantly diminishing their quality of life and overall health. Central to GI motility are the interstitial cells of Cajal (ICC), which play a key role in muscle contractions and neuromuscular transmission. This review highlights the role of ICC in neurointestinal diseases, revealing their association with various GI ailments. Understanding the functions of the ICC could lead to innovative perspectives on the modulation of GI motility and introduce new therapeutic paradigms. These insights have the potential to enhance efforts to combat neurointestinal diseases and may lead to interventions that could alleviate or even reverse these conditions.