Edible mushrooms constitute a small fraction (about 21%) of the total documented macroscopic species of fungi. A lesser proportion of these nutrient-rich delicacies have been identified to confer therapeutic benefits. Although harvesting from the wild was historically the predominant way of obtaining these mushrooms, commercial cultivation of species such as oyster, giant panus, maitake, and button mushrooms is currently a common practice. Edible mushrooms are gaining pharmaceutical relevance over synthetic drugs due to the proven efficacy and harmless effect of their polysaccharide, protein, phenolic, sterol, terpene, and terpenoid constituents. Numerous studies have reported on the ability of mushroom-derived compounds to prevent and/or remedy ailments that are of global concern. Among these ailments are hypercholesterolemia, hepatotoxicity, and immunodeficiency, which are in one way or another linked to the development of other severe health issues. The naturally derived compounds from edible mushrooms have been demonstrated in several in vivo (animal and clinical) and in vitro investigations to combat the organ and/or organ system dysfunctionality associated with the aforementioned abnormalities. Some of the well-studied examples across the class of bioactive compounds found effective against these conditions include β-glucan, lectins, FIPs, eritadenine, lovastatin, ergosterol, and triterpenoids. This chapter provides detailed information on the activities of bioactive compounds derived from edible mushrooms, emphasizing on their potential as hypocholesterolemic, hepatoprotective, and immunomodulatory agents. The wealth of available information on the emphasized therapeutic effects of these active compounds could potentially serve as a basis for their consideration in the development of pharmacognostic products.