The edible and medicinal agaricoid and polyporoid mushrooms (phylum Basidiomycota, order Agaricomycetes) have long been known by humans as valuable food and medicines. They are producers of different groups of high-and lowmolecular weight bioactive compounds (alkaloids, phenolics, polysaccharides, proteins, terpenoids, vitamins etc.) with around 130 therapeutic effects, including neuroprotective. Mushroom-derived biotech products are reported as effective neuroprotectants, however their potential to prevent or mitigate several neurodegenerative pathologies, such as Alzheimer and Parkinson diseases, epilepsy, depression and others has not been fully explored. This review discusses the neuroprotective potential of Agaricomycetes fungi and possibilities for their application as natural neuroprotectants.