Abstract Background Sodium-glucose cotransporter-2 inhibitor (SGLT2i), as a novel oral hypoglycemic therapy of type 2 diabetes mellitus (T2DM), has been proved to benefit cardiac function. However, it remains unknown whether SGLT2i has an impact on coronary plaque characteristics. Purpose The aim of this study was to investigate whether SGLT2i was able to improve coronary plaque composition, burden and inflammation [i.e., fat attenuation index (FAI)] using series coronary computed tomography angiography (CCTA) images among T2DM patients with angina pectoris. Methods T2DM patients presenting with angina pectoris admitted at our center were screened. Eligible patients were those underwent first CCTA within 3 months prior to initiating SGLT2i therapy, and repeated CCTA beyond 6 months after the first CCTA. Those patients not treated with SGLT2i underwent likewise longitudinal CCTA tests were propensity score matching in a 1:1 ratio using age, sex and CCTA time interval. Routine CCTA images were assessed for coronary plaque characteristics using dedicated softwares. Paired or unpaired Student’s t test or Mann–Whitney U test were used for comparing coronary plaque characteristics between series CCTA and patients with or without SGLT2i. The relationships between SGLT2i and changes of plaque characteristics was examined using logistic regression analysis. Results After propensity score matching, a total of 196 T2DM patients with angina pectoris were included (mean age, 60.4±9.2 years; male, 69.9%; SGLT2i treatment, 50%). Time interval between baseline and the last CCTA examinations was 400 (343,496) days. In the SGLT2i group, the non-calcified plaque burden [(39.86±14.30)% vs. (36.84±13.86)%, p=0.002)] and low attenuation non-calcified plaque burden (6.62 [4.11,10.13]% vs. 5.78 [3.40,9.28]%, p=0.042) were significantly decreased between two CCTA images. Whereas, in the non-SGLT2i group, there was no difference with regard to non-calcified and low attenuation non-calcified plaque burden between two CCTA images (all p>0.05). Moreover, changes of total plaque burden and non-calcified plaque burden were higher in the SGLT2i group than the non-SGLT2i group (all p<0.05). Importantly, SGLT2i was associated with total plaque volume (odd ratio=0.594, p=0.024) and non-calcified plaque volume regression (odd ratio=0.619, p=0.042) after adjusting for confounding factors. Conclusion SGLT2i significantly regresses coronary plaque burden, in particularly non-calcified plaque. These findings might explain the observed cardio-protective effect of SGLT2i in large trials.