Mushrooms seem to be a potential source for prebiotics as they contain different polysaccharides such as chitin, hemicellulose, α- and β-glucans, mannans, xylans and galactans. Among mushroom polysaccharides, β-(1→3)-D-glucans, and their peptide/protein derivates (polysaccharide-peptide/protein complexes), proteoglycans are essential prebiotics and found to play vital role in immunomodulating and antitumor activities. These prebiotic compounds display immunomodulating and antitumor activity similar to those effected by immune effector cells such as lymphocytes, macrophages, hematopoietic stem cells, T cells, dendritic cells (DCs) and natural killer (NK) cells that play essential roles in innate and adaptive immunity, resulting in production of biologic response modifiers. Several glucans and heteroglycans were found with their significant immunoenhancing properties which could stimulate the macrophages, splenocytes and thymocytes. Thus this review aims to summarize and explore the potential of mushroom polysaccharides as prebiotics with their antitumor and immunomodulating properties for the development of nutraceutical foods and drugs.