Cluster of differentiation 38 (CD38) is a multifunctional extracellular enzyme on the cell surface with NADase and cyclase activities. CD38 is not only expressed in human immune cells, such as lymphocytes and plasma cells, but also is abnormally expressed in a variety of tumor cells, which is closely related to the occurrence and development of tumors. T cells are one of the important immune cells in the body. As NAD consuming enzymes, CD38, ART2, SIRT1 and PARP1 are closely related to the number and function of T cells. CD38 may also influence the activity of ART2, SIRT1 and PARP1 through the CD38-NAD⁺ axis to indirectly affect the number and function of T cells. Thus, CD38-NAD⁺ axis has a profound effect on T cell activity. In this paper, we reviewed the role and mechanism of CD38⁺ CD4⁺ T cells / CD38⁺ CD8⁺ T cells in cellular immunity and the effects of the CD38-NAD⁺ axis on T cell activity. We also summarized the relationship between the CD38 expression level on T cell surface and disease prediction and prognosis, the effects of anti-CD38 monoclonal antibodies on T cell activity and function, and the role of anti-CD38 chimeric antigen receptor (CAR) T cell therapy in tumor immunity. This will provide an important theoretical basis for a comprehensive understanding of the relationship between CD38 and T cells.