The objective was to assess the protective role of anti-diabetic agent (ADA) in predicting interstitial lung disease (ILD) among patients with diabetes mellitus (DM). We formed a cohort of DM patients between 2009 and 2016 using data from Taiwan. Univariable and multivariable Cox proportion hazards regression models were used to examine the effect of risk factor on the risk of developing ILD, presented as a hazard ratio (HR) with a 95% confidence interval (CI). Cox proportional hazard regression analysis for the risk of DM-associated ILD with joint effect of dipeptidyl peptidase-4 inhibitor (DPP4I), glucagon-like peptide-1 receptor agonist (GLP-1 RA), and sodium-glucose cotransporter 2 inhibitors (SGLT2I) showed that SGLT2I, GLP-1 RA, and DPP-4I had a decreased risk of ILD with adjusted HR of 0.14 (0.11, 0.18), 0.29 (0.24, 0.35), and 0.64 (0.62, 0.67), respectively. DPP4I, GLP-1 RA, and SGLT2I could be considered to be introduced to this DM population for ILD risk reduction in DM, especially with SGLT2I usage.