Escherichia coli NISSLE 1917 (EcN) is a Gram-negative strain with many prominent probiotic properties in the treatment of intestinal diseases such as diarrhea and inflammatory bowel disease (IBD), in particular ulcerative colitis. EcN not only exhibits antagonistic effects on a variety of intestinal pathogenic bacteria, but also regulates the secretion of immune factors in vivo and enhances the ability of host immunity. In this review, the mechanisms of EcN in the remission of inflammatory bowel disease are proposed and recent advances on the functionalized EcN are compiled to provide novel therapeutic strategies for the prevention and treatment of IBD.