Introduction: Administration of butyrate enemas might improve the health status of patients with inflammatory bowel disease (IBD). However, the results seem equivocal. Therefore, this systematic review aimed to assess the effect of sodium butyrate enemas on disease activity index (DAI), endoscopic scores, as well as histological and inflammatory parameters in IBD patients. Methods: The PubMed, Scopus, Web of Science, and Cochrane databases were searched. Randomised controlled trials published in English that assessed the effect of butyrate enemas on DAI, clinical symptoms, inflammatory markers, as well as histological and endoscopic scores in patients with Crohn’s disease (CD) and ulcerative colitis (UC) were included in the analysis. Results: Eight studies involving 227 UC patients were included in this analysis. Only one study reported significant differences in DAI between groups. Besides, butyrate treatment groups did not differ significantly from controls concerning the effect on endoscopic and histological scores. Moreover, butyrate enemas exerted a significant effect on few inflammatory parameters measured in colonic mucosal biopsies. Conclusion: The current evidence is limited and does not support the application of butyrate enemas in UC. There are no reliable data regarding the efficacy of butyrate enemas in CD. The systematic review protocol was registered in the PROSPERO database (CRD42020163654).