Although insulin (INS) injection is widely administrated clinically for the treatment of human type 2 diabetes (T2D), this method cannot effectively prohibit the progressing of diabetes complications. Previously, we demonstrated that daily INS injections could be replaced by transplantations of directly-generated human pluripotent stem cells (dgHPSCs) overexpressing human INS and/or estrogen-related receptor γ (ERRγ) genes. In this investigation, we further revealed that systematic transplantations of dgHPSCs overexpressing INS and/or ERRγ genes could completely replaced the INS injections of T2D patient, and the patient’s blood glucose and HbA1c levels were kept around the normal ranges. Hence, this study provided an important strategy for the eventually cure of human T2D disease through human stem cell and gene therapy.