Core fucosylation, a critical post-translational modification mediated by α1,6-fucosyltransferase (Fut8), is vital in regulating cellular functions and signaling pathways. This glycosylation process is particularly significant in the context of the central nervous system (CNS), where it influences neurodevelopment, synaptic functionality, and the neuroinflammatory response. Aberrations in core fucosylation have been implicated in the pathogenesis of various neuroinflammatory conditions, underscoring its potential as a therapeutic target for neurological disorders. Core fucosylation affects several important signaling molecules and receptors, such as the transforming growth factor-β (TGF-β) receptor, vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), integrins, and glycoprotein 130 (gp130). These molecules are essential for maintaining CNS homeostasis and responding to injury or disease. Furthermore, the dysregulation of core fucosylation has been associated with altered microglial and astrocytic responses to inflammatory stimuli, affecting the progression of neurodegenerative diseases. The modulation of core fucosylation pathways presents a promising avenue for developing novel therapeutic strategies to control neuroinflammation and improve outcomes in patients with neurodegenerative disorders. In conclusion, the intricate relationship between core fucosylation and neuroinflammation offers insights into the molecular mechanisms underlying CNS pathologies and highlights the importance of further research in this area to identify new targets for therapeutic intervention.