Neurodegenerative disorders are driven by complex interactions among glial cells, inflammatory cytokines, and inflammasomes, resulting in progressive neuronal degeneration. Microglia and astrocytes, traditionally considered passive supportive elements, are now recognized as dynamic regulators capable of exerting either neuroprotective or neurotoxic effects depending on the pathological context. Pro-inflammatory cytokines, including interleukin-1β and tumor necrosis factor-α, amplify neuroinflammatory cascades, compromise synaptic integrity, and promote neuronal hyperexcitability. Concurrently, chemokines facilitate the infiltration of peripheral immune cells into the central nervous system, thereby exacerbating inflammatory responses. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome represents a central molecular hub, sensing pathological stimuli such as misfolded protein aggregates and mitochondrial dysfunction, and initiating inflammatory signaling that accelerates disease progression. Therapeutic approaches under investigation include modulation of glial reactivity, selective inhibition of pro-inflammatory cytokine signaling, and pharmacological blockade of inflammasome activation. Advances in combinatorial pharmacotherapy, genome-editing technologies, and nanoparticle-based drug delivery platforms offer the potential for targeted and more effective interventions. Furthermore, high-resolution molecular profiling of glial cell subpopulations is anticipated to elucidate their functional heterogeneity in disease, thereby informing the design of precision therapies that preserve neuronal integrity while mitigating chronic neuroinflammation.