Gastrointestinal system is formed by organs with complex morphology and functions. Digestive tract is not a sterile medium and is exposed to external environment aggressions. As a result, its diseases are complex and encompass a broad spectrum of pathogenic mechanisms and their treatment is often challenging and frequently incurable or chronicity-tending processes are found. In this scenario, stem cells with their differentiation potential and encouraging properties could be helpful. Nowadays Stem Cells have yielded promising results in preclinical studies, some approaches have started clinical development and registered clinical trials are exponentially increasing every year. In 2011, the most advanced programs, involving Crohn’s disease and fistulous disease, have reached phase III of development. Other tested diseases include ulcerative colitis, fecal incontinence or celiac disease. If the preliminary results are confirmed, we think that this therapy may become a clinical reality in the near future. In this chapter, we summarize Stem Cells potential benefits, the current experience and the future perspectives in gastrointestinal system diseases.