The protective effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on the kidneys has been widely recognized. However, limited research has reported the changes in estimated glomerular filtration rate (eGFR) of real-world patients with type 2 diabetes mellitus (T2DM) over time after administration of SGLT-2 inhibitors. This study aimed to reflect the trend of eGFR changes over time in T2DM patients having different baseline eGFR after SGLT-2 inhibitors administration in the real world. A single-center retrospective study was performed in a tertiary public hospital in Beijing, China. In total, 998 outpatients with T2DM who initiated SGLT-2 inhibitors treatment were included in the study. The changes in eGFR, urinary albumin/creatinine ratio (UACR), and glycolipid metabolism indicators were analyzed during the 18-month follow-up period. The eGFR levels significantly decreased to their lowest point (-3.04mL/min/1.73m2) in the first 3months after initiation of SGLT-2 inhibitors treatment, however, gradually returned to the baseline level after 1year. Compared to the subgroup with eGFR >90mL/min/1.73m2, improvements in renal function were more significant in patients with T2DM from the 60 < eGFR ≤90mL/min/1.73m2 and eGFR ≤60mL/min/1.73m2 subgroups after treatment with SGLT-2 inhibitors. Similarly, SGLT-2 inhibitors reduced the UACR in patients with diabetic nephropathy. This study further confirmed the real-world long-term protective effect of SGLT-2 inhibitors on the kidneys of patients with T2DM, which is not related to baseline renal function and blood glucose.