Abstract The connexin family comprises twenty-one distinct protein isoforms, eleven of which are localized within the central nervous system and are expressed by both neuronal and glial cells. These proteins assemble on the cellular membrane to generate a hydrophilic channel measuring approximately 1.5 nanometers in diameter, thereby facilitating the establishment of gap junctions between adjacent cells. The resulting structures, known as connexons and gap junctions or electric synapses, enable the coordinated exchange of functional and metabolic information between neurons and astrocytes. The modification of connexin (Cx) expression and functionality has been found to impact both inflammation and neurodegenerative diseases. Specifically, Cx-mediated hemichannels and channels have been implicated in the development of neurodegenerative disorders. The exacerbation of pathological processes within glial cells results in aberrant regulation of hemichannels, leading to the unregulated release of gliotransmitters and subsequent amplification of the inflammatory response. This highlights the pervasive pathophysiological mechanisms underlying neuroinflammation and suggests the therapeutic potential of targeting Cx-based hemichannels and channels for treatment purposes. This comprehensive review examines the significance of Connexins (Cxs) in both neuroinflammatory and neurodegenerative disorders, where blocking connexin-mediated channels and hemichannels presents potential therapeutic opportunities for treating convulsive and degenerative neurological conditions. The review underscores the crucial role played by Cx-based channels, including gap junctions and electric synapses, as well as hemichannels, or connexons, in the development of neuroinflammation and neurodegeneration. Furthermore, this review delves into the mechanisms underlying Cx-mediated processing of neuro-inflammatory responses.