Chimeric Antigen Receptor T-cell (CAR-T) therapy has revolutionized cancer treatment, particularly in hematologic malignancies, by genetically modifying a patient’s T cells to specifically target and eliminate tumor cells. This groundbreaking approach has led to remarkable clinical outcomes, especially in patients with refractory or relapsed cancers. Over the past few years, CAR-T cell therapy has also been explored for the treatment of autoimmune diseases, including systemic lupus erythematosus (SLE), a complex and chronic autoimmune condition characterized by widespread inflammation and tissue damage. While the potential for CAR-T therapy in autoimmune disorders is significant, its application is accompanied by a range of toxicities that can pose substantial risks to patients, complicating its clinical use. These toxicities arise due to the powerful immune activation induced by CAR-T cells, which can affect various organ systems and result in serious side effects. This paper reviews the mechanisms behind CAR-T therapy-related toxicities, focusing on key adverse events such as Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), hematologic and cellular toxicities, as well as concerns regarding immunogenicity and oncogenic risks. Understanding these toxicities is critical to maximizing the therapeutic benefit of CAR-T therapy while minimizing potential harm to patients.