Diabetic cardiomyopathy (DCM), a severe cardiac complication of diabetes mellitus, is characterized by myocardial dysfunction, fibrosis, and altered metabolic flexibility, independent of hypertension or coronary artery disease. Recent advances in nanobiomaterials have revolutionized the perspective of DCM therapy by enabling precise, targeted, and efficient drug delivery. This chapter explores the epidemiology, classification, and pathophysiology of DCM, emphasizing nanobiomaterial-based targeted therapeutic strategies and their mechanistic pathways. Detailed exploration of the potential of various nanobiomaterial-based therapeutic approaches, including biomimetic and bioinspired nanoparticles, polymeric nanoparticles, and metal and metal oxide nanoparticles, in mitigating DCM pathology. Biomimetic nanoparticles, such as fibroblast growth factor-loaded liposomes and PEGylated nanoliposomes, have shown promise in enhancing myocardial repair and vascular integrity through ultrasound-targeted microbubble destruction (UTMD). Polymeric nanoparticles, particularly those based on poly(lactic-co-glycolic acid) (PLGA) and chitosan, have demonstrated superior drug-delivery capabilities, reducing oxidative stress and improving myocardial function. Furthermore, metal and metal oxide nanoparticles, such as gold (Au), selenium (Se), and cerium oxide (CeO₂), have shown potent antioxidant and anti-inflammatory properties, contributing to myocardial protection and regeneration. Integration of nanotechnology in cardiovascular medicine offers a promising avenue for the development of next-generation therapeutic interventions that ultimately improve outcomes for patients with DCM.