Mushrooms are a nutritious natural resource containing many valuable components such as polysaccharides, phenolic compounds, terpenoids, and bioactive peptides. They are important resources with potential in functional food and pharmacological fields. However, the structural features of fungal cell walls and the low bioavailability of some bioactive compounds limit the effective utilization of these compounds by the human body. Fermentation and bioprocessing techniques may provide important strategies to overcome these limitations and increase the bioavailability and biological activity of bioactive compounds in mushrooms. The fermentation process modifies mushroom cell structures by microorganisms, releasing bioactive compounds and promoting the formation of new metabolites so that fermentation, especially with lactic acid bacteria and yeasts, can enhance the immunomodulatory properties of polysaccharides, increase the antioxidant capacity, and improve gut health by promoting prebiotic effects. Furthermore, enzymatic modifications and biotransformation processes can further enhance the pharmacological activity of mushroom compounds. In this chapter, the techniques of the fermentation and bioprocessing of mushrooms and their effect on the beneficial effects and bioavailability of the mushrooms are discussed in detail. Furthermore, the potential applications of fermented mushrooms in the functional food, nutraceutical, and pharmaceutical industries are emphasized.