Importance <p>Although sodium‒glucose cotransporter-2 (SGLT2) inhibitors have cardiorenal benefits, their efficacy in patients with type 2 diabetes mellitus (T2DM) and chronic coronary syndrome (CCS) undergoing percutaneous coronary intervention (PCI) remains underexplored.</p> Objective <p>To evaluate the cardiorenal protective effects of the SGLT2 inhibitor dapagliflozin in patients with T2DM and CCS receiving PCI.</p> Design, setting, and participants <p>This was a cross-sectional analysis of 1,430 patients from a tertiary hospital database who underwent PCI (January 1, 2018, to March 31, 2022).</p> Main outcomes and measures <p>Cardiac outcomes (PMI/4aMI) and renal outcomes (eGFR and CI-AKI).</p> Results <p>After 1:1 propensity score matching (PSM) (176 dapagliflozin vs. 176 control), the dapagliflozin group showed significantly lower PMI/4aMI rates pre-PSM (39.78% vs. 66.99%; OR 0.862, 95% CI 0.823–0.904; <i>p</i> &lt; 0.001) and post-PSM (39.77% vs. 60.23%; OR 0.660, 95% CI 0.531–0.821; <i>p</i> &lt; 0.001), with sustained significance after adjustment (adjusted OR 0.436, 95% CI 0.285–0.668; <i>p</i> &lt; 0.001). Subgroup analyses highlighted increased protection in patients aged ≥ 65&#xa0;years, those with multivessel disease, and those with higher contrast volumes. Renal outcomes (CI-AKI_ESUR and CI-AKI_KDIGOs) were not significantly different before or after PSM or after adjustment (all <i>p</i> &gt; 0.05).</p> Conclusions and relevance <p>Dapagliflozin exerted robust cardioprotective effects against PMI/4aMI in patients with T2DM and CCS undergoing PCI, particularly among patients in high-risk subgroups, but it did not significantly reduce the risk of CI-AKI. These findings support the peri-PCI use of dapagliflozin to mitigate cardiac risk while highlighting the need for further research to elucidate its renal effects in this population.</p> Graphical abstract <p></p>