Immune checkpoints (ICs), also referred to as co-inhibitory receptors (IRs), are essential for regulating immune cell function to maintain tolerance and prevent autoimmunity. IRs, such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), have been shown to possess immunoregulatory properties that are relevant to various autoimmune diseases and cancers. Tumors are characterized by suppressive microenvironments with elevated levels of IRs on tumor-infiltrating lymphocytes (TILs). Therefore, IR blockade has shown great potential in cancer therapy and has even been approved for clinical use. However, other IRs, including cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), may also represent promising targets for anti-tumor therapy. The increasing importance of IRs in autoimmune diseases has become apparent. In mouse models, TIGIT pathway blockade or TIGIT deficiency has been linked to T cell overactivation and proliferation, exacerbation of inflammation, and increased susceptibility to autoimmune disorders. On the other hand, TIGIT activation has been shown to alleviate autoimmune disorders in murine models. Given these findings, we examine the effects of TIGIT and its potential as a therapeutic target for both autoimmune diseases and cancers. It is clear that TIGIT represents an emerging and exciting target for immunotherapy in these contexts.