Many techniques for isolation, expansion and handling of stem cells are being developed rapidly, and preclinical evidence has shown the possibility to use this technology for refractory diseases in the near future. Among refractory digestive diseases, Crohn's disease and liver cirrhosis may be two main diseases where stem cell therapy can be applied for anti-inflammation and regeneration of tissue. Currently, with respect to these two diseases, clinical trials using hematopoietic stem cells and mesenchymal stem cells from bone marrow or adipose tissue have shown some evidence of clinical benefits to immune modulation, suppression of inflammation and regeneration of functional cells. However, for the development of practical stem cell therapy, we need more data on underlying mechanisms, effective subpopulation of stem cells and its sources, and effective parameters for monitoring and estimation. With technical advances, the research on embryonic and induced pluripotent stem cells will also contribute to the new therapeutic strategies for digestive regenerative medicine. In the future, a variety of stem cell therapies may be therapeutic options for refractory digestive diseases, but many technical challenges remain to be solved.