The human brain undergoes dynamic changes across the human lifespan, from the critical periods of neurodevelopment in early life to structural and functional decline associated with aging. As scientific interest grows in natural interventions via functional foods that support cognitive health, medicinal mushrooms have emerged as promising superfoods with the potential to promote brain development and delay age-related neurodegeneration. This chapter explores the neurobiological benefits of select medicinal mushrooms and their active compounds across the lifespan. It explores the bioactive properties of key medicinal mushrooms such as Hericium erinaceus (Lion’s Mane), Ganoderma lucidum (Reishi), and Cordyceps sinensis and their implications for neurodevelopmental and neuroprotective processes attributed to their rich neuroactive compounds such as hericenones, erinacines, polysaccharides, terpenoids, and antioxidants that have demonstrated the ability to modulate neurogenesis, enhance nerve growth factor (NGF) production, reduce oxidative stress, and regulate inflammatory pathways. During early brain development, these actions may support cognitive maturation, synaptic plasticity, and the formation of robust neural networks for memory formation while in the aging populations they offer protection against cognitive decline, improve mood and sleep, and delay the onset of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. This chapter reviews evidence from experimental, clinical, and ethnobotanical studies to examine how medicinal mushrooms influence brain structure and function throughout life, ultimately demonstrating medicinal mushrooms as promising natural agents in promoting cognitive vitality from infancy through old age.