By identifying foreign antigens expressed on the surface of tumor cells, the immunological system contributes significantly to limiting the dissemination of malignant cancers and aiding in the prevention of tumor development. Natural Killer T (NKT) cells are a type of immune cell that resembles both T cells and NK cells. Despite the fact that NKT cells are a small population of immune cells, they are thought to function as a link between the innate and adaptive immune systems, and as such, they play an important role in cell immunity maintenance. There are two types of NKT cells, including type I and type II. Activated type I NKT cells are crucial in antitumor activity through the direct killing of tumor cells expressing CD1d or through the direct release of different cytokines, while type II NKT cells inhibit the immunological response. Anergy and a lack of responsiveness occur in response to the overstimulation of type I NKT cells. Various mechanisms, such as the administration of α -GalCer or IL-12, can be used to stimulate and harness type I NKT cells in tumor immunotherapy. Tumors, on the other hand, have evolved various mechanisms to suppress type I NKT cells or convert them into more immunosuppressive subsets such as TH2-like and Treg-like NKT cells, making their use difficult and limited. As a result, a number of approaches have been developed to take advantage of the antitumor activity of type I NKT cells in preclinical and clinical studies. Herein, we discuss the biology of diverse NKT cell subsets, their antitumor mechanism, and anergy. Ultimately, various NKT cell-based immunotherapy in cancer and clinical trials are summarized.