Since ancient times, medicinal mushrooms have been traditionally used as a health food or supplement for the prevention and cure of a range of health-statuses or diseases, such as overt inflammation, atherosclerosis, cancer, hypertension, diabetes and others. We concentrate in this review on the effect and putative mechanism of action of glucans harvested from fungi on inflammatory bowel disease (IBD) and colitis associated cancer. Many scientists including our own group have examined the immunomodulating effect of isolated polysaccharides-glucans in general and specifically in inflammation associated with cancer. In this manuscript we reviewed the sources, the chemical composition and medicinal properties of polysaccharides extracted from edible mushrooms. In addition we brought insights into their putative mechanisms of action behind each health-promoting activity of these interesting biomolecules. The preventive and therapeutic effects of the medicinal mushrooms and their components have been well documented in mouse and rat model systems and in cancer cell lines being the most striking effects reported to their anti-inflammatory and antitumor effect. Their anticancer effects were demonstrated mainly in in vitro and in vivo experimental systems but a very limited number of studies have been conducted in human populations. We can summarize that oral consumption of several mushrooms glucans is an efficient treatment to prevent colitis-associated dysplasias through modulation of mucosal inflammation and cell proliferation. Identifying new food-derived isolates and understanding their mechanisms of action are the main challenges in using mushrooms glucans for therapeutic purposes in the field of IBD and associated cancer. Only an in-depth understanding of the mechanism of action and cross-talk between the inflammatory cell, epithelial cell and fungi derived glucans on which we have a based structural knowledge will lead to well designed intervention clinical human studies to test the efficacy of these molecules on intestinal inflammation and colitis associated cancer