The last century has seen an increase in our life expectancy. As a result, various age-related diseases, such as neurodegenerative diseases (NDs), have emerged, representing new challenges to society. Oxidative stress (OS), a condition of redox imbalance resulting from excessive production of reactive oxygen species, represents a common feature that characterizes the brains of elderly people, thus contributing to NDs. Consequently, antioxidant supplementation or dietary intake of antioxidant-containing foods could represent an effective preventive and therapeutic intervention to maintain the integrity and survival of neurons and to counteract the neurodegenerative pathologies associated with aging. Food contains numerous bioactive molecules with beneficial actions for human health. To this purpose, a wide range of edible mushrooms have been reported to produce different antioxidant compounds such as phenolics, flavonoids, polysaccharides, vitamins, carotenoids, ergothioneine, and others, which might be used for dietary supplementation to enhance antioxidant defenses and, consequently, the prevention of age-related neurological diseases. In this review, we summarized the role of oxidative stress in age-related NDs, focusing on the current knowledge of the antioxidant compounds present in edible mushrooms, and highlighting their potential to preserve healthy aging by counteracting age-associated NDs.