Natural killer (NK) cells, a major component of the innate immune system, have prominent immunoregulatory, antitumor proliferation, and antiviral activities. NK cells act as a double-edged sword with therapeutic potential in neurological autoimmunity. Emerging evidence has identified NK cells are involved in the development and progression of neuroimmunological diseases such as multiple sclerosis, neuromyelitis optica spectrum disorders, autoimmune encephalitis, Guillain-Barré Syndrome, chronic inflammatory demyelinating polyneuropathy, myasthenia gravis, and idiopathic inflammatory myopathy. However, the regulatory mechanisms and functional roles of NK cells are highly variable in different clinical states of neuroimmunological diseases and need to be further determined. In this review, we summarize the evidence for the heterogenic involvement of NK cells in the above conditions. Further, we describe cutting-edge NK-cell-based immunotherapy for neuroimmunological diseases in preclinical and clinical development and highlight challenges that must be overcome to fully realize the therapeutic potential of NK cells.