Nowadays macrofungi are distinguished as important natural resources of immunomodulating and anticancer agents and with regard to the increase in diseases involving immune dysfunction, cancer, autoimmune conditions in recent years, applying such immunomodulator agents especially with the natural original is vital. These compounds belong mainly to polysaccharides especially beta-d-glucan derivates, glycopeptide/protein complexes (polysaccharide-peptide/protein complexes), proteoglycans, proteins and triterpenoids. Among polysaccharides, beta(1-->3)-d-glucans and their peptide/protein derivates and among proteins, fungal immunomodulatory proteins (Fips) have more important role in immunomodulating and antitumor activities. Immunomodulating and antitumor activity of these metabolites related to their effects to act of immune effecter cells such as hematpoietic stem cells, lymphocytes, macrophages, T cells, dendritic cells (DCs), and natural killer (NK) cells involved in the innate and adaptive immunity, resulting in the production of biologic response modifiers. In this review we have introduced the medicinal mushrooms' metabolites with immunomoduling and antitumor activities according to immunological evidences and then demonstrated their effects on innate and adaptive immunity and also the mechanisms of activation of immune responses and signaling cascade. In addition, their molecular structure and their relation to these activities have been shown. The important instances of these metabolites along with their immunomodulating and/or antitumor activities isolated from putative medicinal mushrooms are also introduced.