Interleukin-6 (IL-6) is a versatile cytokine crucial for immune response modulation, inflammation regulation, and various physiological processes. Dysregulated IL-6 is closely associated with many diseases, making it a key research and therapeutic target. Elevated IL-6 levels in the central nervous system worsen neuroinflammation in neurodegenerative diseases by activating microglia and astrocytes and releasing pro-inflammatory cytokines and neurotoxic molecules. Mesenchymal stem cells (MSCs) show promise in modulating neuroinflammation by regulating IL-6 levels, effectively suppressing pro-inflammatory cytokines while promoting anti-inflammatory factors. This review provides a comprehensive overview of IL-6's involvement in neurological disorders, examining endogenous IL-6 and IL-6 derived from MSCs. It explores IL-6's mechanisms affecting neuronal function, survival, and immune modulation in the central nervous system, and discusses the potential of MSC-derived IL-6 in neuroregeneration and neuroprotection. By elucidating IL-6's interplay with neurological pathologies, this review offers insights into novel therapeutic strategies targeting IL-6 signaling pathways for neurological disorders.Interleukin-6 (IL-6) is a versatile cytokine crucial for immune response modulation, inflammation regulation, and various physiological processes. Dysregulated IL-6 is closely associated with many diseases, making it a key research and therapeutic target. Elevated IL-6 levels in the central nervous system worsen neuroinflammation in neurodegenerative diseases by activating microglia and astrocytes and releasing pro-inflammatory cytokines and neurotoxic molecules. Mesenchymal stem cells (MSCs) show promise in modulating neuroinflammation by regulating IL-6 levels, effectively suppressing pro-inflammatory cytokines while promoting anti-inflammatory factors. This review provides a comprehensive overview of IL-6's involvement in neurological disorders, examining endogenous IL-6 and IL-6 derived from MSCs. It explores IL-6's mechanisms affecting neuronal function, survival, and immune modulation in the central nervous system, and discusses the potential of MSC-derived IL-6 in neuroregeneration and neuroprotection. By elucidating IL-6's interplay with neurological pathologies, this review offers insights into novel therapeutic strategies targeting IL-6 signaling pathways for neurological disorders.