For centuries, medicinal mushrooms have played a vital role in traditional healing systems across the globe, prized for their wide-ranging therapeutic properties, particularly their potential to support brain health. In response to the escalating global burden of mental health disorders and neurodegenerative diseases, there has been a renewed focus on natural, functional foods as promising preventive and therapeutic agents. This chapter explores medicinal mushrooms’ historical and cultural significance in diverse regions—including Asia, Europe, Africa, the Americas, and Oceania—and connects these long-standing practices with modern consumption patterns. The global medicinal mushroom market is expanding significantly, propelled by rising consumer interest in natural cognitive enhancers and stress-relief agents. Today, these fungi are available in a variety of formats such as teas, tinctures, powders, and functional food products, with species like Hericium erinaceus (Lion’s Mane), Ganoderma lucidum (Reishi), and Cordyceps sinensis emerging as key players in cognitive wellness. Growing scientific research continues to substantiate traditional applications by isolating bioactive constituents—polysaccharides, triterpenoids, and hericenones—demonstrating neuroprotective, anti-inflammatory, and cognitive-enhancing properties. Additionally, current trends reflect the integration of medicinal mushrooms into contemporary dietary lifestyles, including plant-based, ketogenic, and paleo regimens, as well as their rising prominence in the brain health and nootropic markets. Future directions emphasize the need for rigorous clinical trials, improved bioavailability of active constituents, standardized regulatory frameworks, and the development of personalized interventions. As the intersection between ethnomycology and modern neuroscience deepens, medicinal mushrooms are gaining recognition as valuable tools in the global pursuit of enhanced cognitive resilience and emotional well-being.