Infections affecting the nervous system require a rapid expansion of effective therapeutic strategies. The emergence of new viral pathogens continues to pose a substantial threat to brain health worldwide, as evidenced by the recent pandemic. The neurological consequences of infections are often characterized by protein aggregation, mitochondrial dysfunction, neuroinflammation, and oxidative stress, pathological hallmarks that compromise neuronal integrity and cognitive function. In this landscape, natural bioactive compounds are gaining increasing attention as promising candidates for therapeutic support. Among these, edible and medicinal mushrooms represent an emerging frontier in neuroprotection. Species such as Lentinula edodes, Tremella fuciformis, Auricularia auricula-judae, Pleurotus eryngii, Agaricus bisporus, Ganoderma lucidum, Inonotus obliquus, and Hericium erinaceus are recognized for their unique ability to produce bioactive molecules with potent antioxidant, anti-inflammatory, and neuroprotective activities. This review explores for the first time the complex interplay between infections and neurological disorders, highlighting the potential of mushrooms not only as functional foods but also as complementary allies in safeguarding brain health.