Lentinula edodes (L. edodes) is the globally second most widely consumed mushroom that is well-known for its therapeutic potential and is a commonly used experimental fungus model. This review was focused on the benefits, efficacy, and potential mechanism of action of the extracts from L. edodes as described in the previous studies. With limited information on the health-related benefits of L. edodes, several investigators have now diverted their attention towards this macrofungus. Several studies have now revealed its antitumor, immune-modulating, antitumor, antiviral, antimicrobial, cholesterol-regulating, anti-atherosclerotic, antidiabetic, antioxidant, and homocysteinemia activities.