Fungal bioactive polysaccharides are well known and have been widely used in Asia as a part of the traditional diet and medicine. In fact, some biopolymers (mainly β-glucans or glycoconjugate) have already made their way to the market as antitumor or immunostimulating drugs. In the last decades, the relationship between structure and activity of polysaccharides and their detailed mode of action have been the core of intense research to understand and utilize their medicinal properties. Most of the antitumor polysaccharides belong to conserved β-glucans, with a linear β-(1→3)-glucan backbone and attached β-(1→6) branch. Structurally different β-glucans appear to have different affinities toward their receptors and thus generate markedly different host responses. However, their antitumor activities are mainly influenced by molecular mass, degree of branching, conformation, and structure modification of the polysaccharides. β-Glucans act on several immune receptors including Dectin-1, complement receptor (CR3) and TLR-2/6, then trigger both innate and adaptive response and enhance opsonic and nonopsonic phagocytosis. Various receptor interactions explain the possible mode of actions of polysaccharides.