Ganoderma lucidum (GL) is a medicinal mushroom which is highly appreciated in Traditional Chinese Medicine and has also been extensively studied in the contemporary world. Scientific investigations have established various medicinal and nutraceutical activities of this medicinal mushroom. The fungus is known to be a repository of numerous bioactive metabolites including terpenoids, polysaccharides, proteins and peptides, nucleotides, fatty acids, steroids, vitamins and minerals. Among these biologically active compounds, the most researched class of compounds are terpenoids and polysaccharides. Consequently, several review articles describing the pharmacological properties of terpenoids and polysaccharides derived from GL are available. Amidst the proteins isolated from GL, Ling Zhi-8 (LZ-8) is the most studied protein. However, no review is available to the best of our knowledge, although there are numerous studies pertaining to the bioactivities of this protein and its recombinant form. The protein LZ-8 has been reported to exhibit immunomodulatory, mitogenic, antitumor, anti-cancer, anti-diabetic and anti-osteoporotic activities. Thus, in this article we intend to summarize the research conducted so far regarding the therapeutic effects and mechanisms of action of LZ-8 protein isolated from GL and also its recombinant form. This shall enable a comprehensive review on the research conducted regarding LZ-8 protein until now.