Mushrooms are experiencing a kind of renaissance as a part of the contemporary human diet. These valuable organisms are more than food, they fit in perfectly as a novel market group known as nutra-mycoceuticals. Immune-balancing mushroom dietary fibers and secondary metabolites such as polyphenols are the main focus of the healthcare industry. Wellness and cosmetic companies are increasingly using mushroom extracts rich in these ingredients. This review considers the basic molecular immunomodulatory mechanisms of action of the most commonly used mushroom dietary fibers, β-glucans. The literature data on their bioavailability, metabolic transformations, preclinical and human clinical research, and safety are discussed. Immunomodulatory mechanisms of polyphenol ingredients are also considered. These molecules present great potential in the design of the new immunity balancer formulations according to their widespread structural diversity. Finally, we draw attention to the perspectives of modern trends in mushroom nutraceutical and cosmeceutical formulations to strengthen and balance immunity.