Cardiac fibrosis is a key pathological substrate that drives diastolic dysfunction, arrhythmogenesis, and heart failure progression across a spectrum of cardiometabolic disorders. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, initially developed for glucose lowering, have demonstrated pleiotropic effects on myocardial structure, notably attenuating fibrotic remodeling. Experimental models of diabetes, hypertension, ischemia, and cardiotoxicity consistently show that SGLT2 inhibitors mitigate interstitial and perivascular fibrosis through modulation of oxidative stress, mitochondrial function, autophagy, and canonical profibrotic signaling cascades, including TGF-β/Smad, STAT3, and mTOR. These actions are largely preserved in non-diabetic settings and appear to extend beyond hemodynamic or glycemic benefits. Clinical data, including cardiac magnetic resonance–based assessments, support the notion of diffuse fibrosis regression, particularly in heart failure with preserved ejection fraction and diabetic cardiomyopathy. Moreover, reductions in serum collagen biomarkers and improvements in myocardial energetics further substantiate their antifibrotic capacity. Nonetheless, fibrosis-specific endpoints remain underrepresented in major cardiovascular outcome trials, and histological validation in human tissue is lacking. Integrating artificial intelligence–driven fibrosis quantification, spatial transcriptomics, and high-resolution imaging may refine phenotyping and enable precision antifibrotic therapy. Whether fibrosis regression translates into durable clinical benefit remains an open question. This review comprehensively synthesizes the mechanistic, translational, and clinical evidence supporting the role of SGLT2 inhibitors as modulators of cardiac fibrosis across diverse cardiovascular disease states.