Abstract: Fungal phytochemicals derived from higher fungi, particularly those from the culinary-medicinal genus Hericium, have gained significant attention in drug discovery and healthcare. This review aims to provide a comprehensive analysis of the chemical structures, biosynthetic pathways, biological activities, and pharmacological properties of monomeric compounds isolated from Hericium species. Over the past 34 years, 253 metabolites have been identified from various Hericium species, including cyathane diterpenes, alkaloids, benzofurans, chromenes, phenols, pyrones, steroids, and other miscellaneous compounds. Detailed investigations into the biosynthesis of erinacines, a type of cyathane diterpene, have led to the discovery of novel cyathane diterpenes. Extensive research has highlighted the biological activities and pharmacological properties of Hericium-derived compounds, with particular emphasis on their neuroprotective and neurotrophic effects, immunomodulatory capabilities, anti-cancer activity, antioxidant properties, and antimicrobial actions. Erinacine A, in particular, has been extensively studied. Genomic, transcriptomic, and proteomic analyses of Hericium species have facilitated the discovery of new compounds and provided insights into enzymatic reactions through genome mining. The diverse chemical structures and biological activities of Hericium compounds underpin their potential applications in medicine and as dietary supplements. This review not only advances our understanding of Hericium compounds but also encourages further research into Hericium species within the realms of medicine, health, functional foods, and agricultural microbiology. The broad spectrum of compound types and their diverse biological activities present promising opportunities for the development of new pharmaceuticals and edible products.