Fungal endophytes are a group of fungi that reside in plant tissues and show a symbiotic relationship with the host plants. They protect against pathogens and increase food availability without causing any harmful effects on the host plant. Fungal endophytes are known to produce a wide range of bioactive compounds with several biological activities, including neuroprotective effects. Neurodegenerative disorders lead to miscommunication between nerve cells, damage or loss in structure and function of the central nervous system (CNS) or peripheral nervous system (PNS). Reactive oxygen species, neuroinflammation, protein degradation or aggregation, familial history, mutation in mitochondrial genes, and aging contribute to neurodegenerative disorders. Plant-associated fungal endophytes produce bioactive compounds, which show anti-neuroinflammatory, antioxidant, and anti-cholinesterase activities. Several pro-inflammatory (TNF-α and NF-κB) and depressant (serotonin, dopamine, and noradrenaline) molecules or neuronal signaling pathways leading to neurodegenerative disorders are known to be inhibited or down-regulated by fungal endophyte-derived bioactive compounds. Therefore, bioactive compounds produced from fungal endophytes could be a promising approach to treating various healthailments. The present chapter discusses selected fungal endophyte-derived potential bioactive compounds with neuroprotective effects for managing neurodegenerative disorders.