Endoscopic submucosal dissection (ESD) is a curative treatment for superficial esophageal cancer with distinct advantages. However, esophageal stenosis after ESD remains a tough problem, especially after large circumferential proportion of esophageal mucosa is removed, which limits the wide use of ESD, especially in circumferential lesions. In this scenario, preventive procedures are highly recommended against post-ESD esophageal stenosis. However, the efficacy and safety of traditional prophylactic methods (steroids, metal and biodegradable stents, balloon dilation, radial incision, etc .) are not satisfactory and novel strategies need to be developed. Regenerative medicine has been showing enormous potential in the reconstruction of organs including the esophagus. In this review, we aimed to describe the current status of regenerative medicine in prevention of post-ESD esophageal stenosis. Cell injection, cell sheet transplantation, and extracellular matrix implantation have been proved effective. However, numerous obstacles still exist and further studies are necessary.