The inflammatory bowel diseases (IBDs) are chronic inflammatory conditions, which are increasing in prevalence worldwide. The IBDs are thought to result from an aberrant immune response to gut microbes in genetically susceptible individuals. Dysbiosis of the gut microbiome, both functional and compositional, promotes patient susceptibility to colonization by pathobionts. Manipulating gut microbial communities and gut microbiota-immune system interactions to restore gut homeostasis or reduce inflammation are appealing therapeutic models. We discuss the therapeutic potential of precision microbiota editing, natural and engineered probiotics, the use of gut microbiota-derived metabolites in colitogenic phenotypes, and intestinal stem cells, in maintaining gut microbiota balance, restoring the mucosal barrier, and having positive immunomodulatory effects in experimental IBD. This review highlights that we are only just beginning to understand the complexity of the microbiota and how it can be manipulated for health benefits, including treatment and prevention of the clinical IBDs in future.