Inflammatory bowel diseases (IBD) are modern diseases, with incidence rising around the world. They are associated with perturbation of the intestinal microbiota, and with alteration and crossing of the mucus barrier by the commensal bacteria that feed on it. In the process of mucus catabolism and invasion by gut bacteria, carbohydrate-active enzymes (CAZymes) play a critical role since mucus is mainly made up by O- and N-glycans. Moreover, the occurrence of IBD seems to be associated with low-fiber diets. Conversely, supplementation with oligosaccharides, such as human milk oligosaccharides (HMOs), which are structurally similar to intestinal mucins and could thus compete with them towards bacterial mucus-degrading CAZymes, has been suggested to prevent inflammation. In this mini-review, we will establish the current state of knowledge regarding the identification and characterization of mucus-degrading enzymes from both cultured and uncultured species of gut commensals and enteropathogens, with a particular focus on the present technological opportunities available to further the discovery of mucus-degrading CAZymes within the entire gut microbiome, by coupling microfluidics with metagenomics and culturomics. Finally, we will discuss the challenges to overcome to better assess how CAZymes targeting specific functional oligosaccharides could be involved in the modulation of the mucus-driven cross-talk between gut bacteria and their host in the context of IBD.