Interleukin-6 (IL-6) is a versatile cytokine involved in immune response, inflammation, and various physiological processes. Dysregulated IL-6 is linked to numerous diseases, including neurodegenerative disorders. Elevated IL-6 levels in the central nervous system worsen neuroinflammation by activating microglia and astrocytes, releasing pro-inflammatory cytokines, and weakening the blood-brain barrier. Mesenchymal stem cells (MSCs) can modulate neuroinflammation by regulating IL-6 levels, suppressing pro-inflammatory cytokines, and promoting anti-inflammatory factors. This review explores IL-6's role in neurological disorders, focusing on its involvement in neuroinflammation, neurodegeneration, and neuroprotection. It also discusses the potential of MSC-derived IL-6 in neuroregeneration and neuroprotection. IL-6 signaling pathways, including classical and trans-signaling, are crucial for immune response, inflammation, and cellular proliferation. MSCs can influence IL-6 production through autocrine and paracrine signaling, as well as feedback mechanisms. MSCs have anti-inflammatory effects, reducing IL-6 levels and promoting tissue repair. In neuroinflammation, MSCs can downregulate IL-6 by activated microglia and astrocytes, enhancing neuroprotection. IL-6 derived from MSCs plays a key role in neuroprotection by reinforcing neuronal survival and providing protection against various insults. The review highlights the importance of targeting IL-6 signaling pathways in the treatment of neurological disorders.Interleukin-6 (IL-6) is a versatile cytokine involved in immune response, inflammation, and various physiological processes. Dysregulated IL-6 is linked to numerous diseases, including neurodegenerative disorders. Elevated IL-6 levels in the central nervous system worsen neuroinflammation by activating microglia and astrocytes, releasing pro-inflammatory cytokines, and weakening the blood-brain barrier. Mesenchymal stem cells (MSCs) can modulate neuroinflammation by regulating IL-6 levels, suppressing pro-inflammatory cytokines, and promoting anti-inflammatory factors. This review explores IL-6's role in neurological disorders, focusing on its involvement in neuroinflammation, neurodegeneration, and neuroprotection. It also discusses the potential of MSC-derived IL-6 in neuroregeneration and neuroprotection. IL-6 signaling pathways, including classical and trans-signaling, are crucial for immune response, inflammation, and cellular proliferation. MSCs can influence IL-6 production through autocrine and paracrine signaling, as well as feedback mechanisms. MSCs have anti-inflammatory effects, reducing IL-6 levels and promoting tissue repair. In neuroinflammation, MSCs can downregulate IL-6 by activated microglia and astrocytes, enhancing neuroprotection. IL-6 derived from MSCs plays a key role in neuroprotection by reinforcing neuronal survival and providing protection against various insults. The review highlights the importance of targeting IL-6 signaling pathways in the treatment of neurological disorders.