Natural killer T (NKT) cells are a unique subset of T lymphocytes that recognize non-classical antigen-presenting molecules, specifically CD1d, and respond to glycolipid antigens. Unlike conventional T lymphocytes and other regulatory T cells (Tregs), NKT cells can either enhance or suppress immune responses by producing Th1 or Th2 cytokines. This review explores the diverse roles of NKT cells in various disease models, their ability to modulate immunity, and the potential for using them as a novel form of immunotherapy. NKT cells have been implicated in the regulation of autoimmune diseases, cancer, and host defense. They can suppress tissue destruction, influence autoimmunity, and play a role in antitumor responses. In autoimmune diseases, NKT cells can promote or suppress immune responses, depending on the context. In cancer, NKT cells can enhance or suppress tumor immunity, and their activation by α-galactosylceramide (α-GalCer) has shown promise in clinical trials. NKT cells also participate in host defense against bacterial, viral, and parasitic infections, although their role can be both stimulatory and suppressive. The regulatory function of NKT cells is likely influenced by the type of signals they receive, the subset of NKT cells present, and the microenvironmental factors. Future clinical applications of NKT cell-based immunotherapy may benefit from a better understanding of the factors that activate and modulate NKT cells.Natural killer T (NKT) cells are a unique subset of T lymphocytes that recognize non-classical antigen-presenting molecules, specifically CD1d, and respond to glycolipid antigens. Unlike conventional T lymphocytes and other regulatory T cells (Tregs), NKT cells can either enhance or suppress immune responses by producing Th1 or Th2 cytokines. This review explores the diverse roles of NKT cells in various disease models, their ability to modulate immunity, and the potential for using them as a novel form of immunotherapy. NKT cells have been implicated in the regulation of autoimmune diseases, cancer, and host defense. They can suppress tissue destruction, influence autoimmunity, and play a role in antitumor responses. In autoimmune diseases, NKT cells can promote or suppress immune responses, depending on the context. In cancer, NKT cells can enhance or suppress tumor immunity, and their activation by α-galactosylceramide (α-GalCer) has shown promise in clinical trials. NKT cells also participate in host defense against bacterial, viral, and parasitic infections, although their role can be both stimulatory and suppressive. The regulatory function of NKT cells is likely influenced by the type of signals they receive, the subset of NKT cells present, and the microenvironmental factors. Future clinical applications of NKT cell-based immunotherapy may benefit from a better understanding of the factors that activate and modulate NKT cells.