Systemic erythematosus lupus (SLE) is a classic autoimmune disease characterized by multiple autoantibodies and immune-mediated tissue damage. The etiology of this disease is still unclear. A new drug, Belimumab, which acts against the B-lymphocyte stimulator (BLyS), can effectively improve the condition of SLE patients, but it cannot resolve all SLE symptoms. The discovery of novel, precise therapeutic targets is urgently needed. It is well known that abnormal T cell function is one of the most crucial factors contributing to the pathogenesis of SLE. Protein post-translational modifications (PTMs), including phosphorylation, glycosylation, acetylation, methylation, ubiquitination, and SUMOylation, have been emphasized for their roles in activating protein activity, maintaining structural stability, regulating protein-protein interactions and mediating signaling pathways, in addition to other biological functions. Summarizing the latest data in this area, this review focuses on the potential roles of diverse PTMs in regulating T cell function and signaling pathways in SLE pathogenesis, with the goal of identifying new targets for SLE therapy.