Interleukin-6 (IL-6) is a multifunctional cytokine that plays a criticalrole in immune regulation, host defense, and tissue repair. Within thecentral nervous system (CNS), IL-6 contributes to both neuroprotectionand neuroinflammation, depending on the signaling pathway involved;classic signaling, trans-signaling, or trans-presentation. Dysregulation ofIL-6, particularly through sustained overexpression, disrupts the blood–brain barrier (BBB) integrity, promotes glial activation, and amplifieschronic inflammation, thereby contributing to the pathophysiology ofnumerous neurological disorders.This review aims to evaluate the role of IL-6 in neuroinflammatoryprocesses and its clinical implications across a spectrum of neurologicaldiseases. It focuses on the therapeutic potential and safety profileof IL-6 inhibitors, particularly tocilizumab and satralizumab. Keyconditions discussed include neuromyelitis optica spectrum disorder(NMOSD), myelin oligodendrocyte glycoprotein-associated disease(MOGAD), autoimmune encephalitis (AE), neuro-Behçet’s disease(NBD), myasthenia gravis (MG), epilepsy, multiple sclerosis (MS), andAlzheimer’s disease (AD).Clinical trials have demonstrated the efficacy of IL-6 receptor blockadein reducing relapse rates in NMOSD, leading to regulatory approvals.Promising off-label results have also been reported in treatment-resistantcases of MOGAD, epilepsy, and autoimmune conditions. However,IL-6 inhibition carries risks such as serious infections and paradoxicalinflammatory reactions.Targeting the IL-6 pathway represents a significant advancement inneuroimmunology, offering new therapeutic opportunities for otherwiserefractory conditions. Future research should focus on large-scalerandomized controlled trials and the development of IL-6 inhibitorscapable of crossing the BBB to enhance CNS-specific efficacy. Costrelatedaccessibility also remains a major challenge for broader clinicalapplication.Keywords: Interleukin-6, neuroinflammation, satralizumab, tocilizumab