Inflammatory bowel disease is a chronic condition characterized by recurrent intestinal inflammation. Its etiopathogenesis is driven by a series of events that disrupt the mucosal barrier, alter the healthy balance of intestinal microbiota, and abnormally stimulate intestinal immune responses. Therefore, numerous studies suggest the use of short-chain fatty acids and their immunomodulatory effects as a therapeutic approach in this disease. The objective of this systematic review was to synthesize previous evidence on the relevance and therapeutic use of short-chain fatty acids, particularly butyrate, in the immune regulation of inflammatory bowel disease. This systematic review of articles linking inflammatory bowel disease with short-chain fatty acids was conducted according to the PRISMA-2020 guidelines. The Medline and the Web of Science databases were searched in August 2024. The risk of bias was assessed using the Joanna Briggs Institute checklists. A total of 1460 articles were reviewed, of which, 29 met the inclusion criteria. Short-chain fatty acids, particularly butyrate, play a critical role in the regulation of intestinal inflammation and can be used as a strategy to increase the levels of short-chain fatty acid-producing bacteria for use in therapeutic approaches.