<p>Diabetes and its complications represent a global burden to human health. Among diabetic microvascular and macrovascular complications, diabetic cardiomyopathy (DCM) remains the primary and most prevalent condition leading to decreased cardiomyocyte function and risk of cardiac morbidities and mortality rate. Decreased cardiomyocyte function is mediated by the pathophysiological mechanisms broadly including glucotoxicity, endoplasmic reticulum stress, metabolic insulin signaling, mitochondrial dysfunction, oxidative stress, renin–angiotensin–aldosterone system activation, impaired calcium handling, apoptosis of cardiomyocytes, and cardiac lipotoxicity, which could be favorable targets for new therapeutic interventions. Currently, the treatment given in DCM is not enough in terms of cure; therefore, there is a need to introduce novel potential treatment options. Not any single therapeutic agent would treat DCM completely, so a variety of approaches are needed. The approaches can be a balanced outset of lifestyle modification, use of herbal and nutraceuticals, glucose control medication, antioxidants, angiotensin receptor blockers, and angiotensin-converting enzyme inhibitors to reduce the progression of DCM and effectively treat the patients. In the current review, emphasis has been made on the molecular mechanisms involved in the onset of DCM. We summarize the findings from preclinical and clinical studies including non-pharmacological strategies that might provide the directions for the development of targeted treatment approaches. Additionally, we discuss the novel and emerging therapeutic targets aimed at the management of DCM.</p>