Irisin, a myokine discovered in recent years, has been widely confirmed to exert cardioprotective effects. This review comprehensively elaborates on the molecular mechanisms of Irisin in diabetic cardiomyocytes and its close associations with pathophysiological processes such as disordered glycolipid metabolism, oxidative stress, and autophagy. In terms of regulating glycolipid metabolism, Irisin significantly improves energy metabolism in cardiomyocytes by activating the AMPK signaling pathway, thereby reversing diabetes-induced metabolic abnormalities. It promotes the browning of white adipose tissue (WAT), a process in which subcutaneous fat demonstrates a greater propensity to brown compared to visceral fat, thereby enhancing energy expenditure and exerting anti-inflammatory effects. These browned adipocytes secrete bioactive substances such as FGF and adiponectin, which further contribute to metabolic balance. Meanwhile, Irisin reduces the glucolipotoxic burden on pancreatic β-cells: by modulating signaling pathways including PI3K/AKT and AMPK, it not only inhibits β-cell apoptosis but also improves their function and morphology. It enhances insulin secretion by regulating key proteins including Glut2, Glk, and Pdx1 through the AMPK pathway. Additionally, Irisin accelerates the oxidation of free fatty acids (FFA) via activation of pathways such as PPARα, ameliorates insulin resistance, and thus optimizes the metabolic environment of cardiomyocytes. In the context of cellular stress regulation, Irisin exhibits potent antioxidant properties. It not only directly counteracts the accumulation of reactive oxygen species (ROS) to alleviate oxidative damage but also inhibits ferroptosis by upregulating the MITOL/MARCH5 signaling axis, thereby helping to maintain mitochondrial homeostasis. Regarding endoplasmic reticulum stress (ERS), Irisin downregulates key proteins including GRP78 and PERK, thus mitigating ERS-induced cardiomyocyte apoptosis and fibrosis—a protective mechanism that has also been validated in other diseases such as pancreatitis and osteoporosis. In maintaining the balance between autophagy and cell death, Irisin sustains cellular homeostasis by coordinating both mitochondrial-targeted autophagy and non-selective autophagy. It promotes FUNDC1-mediated mitophagy to support mitochondrial turnover and ensure proper organelle function. At the same time, it suppresses excessive autophagy-induced cell damage through pathways such as PI3K/AKT/mTOR. In terms of apoptosis regulation, Irisin downregulates pro-inflammatory factors (e.g., TNF-α, IL-6) and apoptosis-related proteins such as Caspase-3, while upregulating the anti-apoptotic protein Bcl-2. It inhibits cardiomyocyte apoptosis through multiple signaling pathways, including AMPK/mTOR and miR-19b/PTEN. In summary, Irisin plays a crucial protective role in improving metabolic disorders, reducing cellular stress damage, and regulating cell death in diabetic cardiomyopathy (DCM) through multi-target and multi-pathway synergistic mechanisms. Its diverse actions provide an important theoretical basis and potential therapeutic targets for the clinical prevention and treatment of DCM. However, further research is needed to clarify its systemic effects, the safety of clinical interventions, and optimal treatment strategies to fully realize its therapeutic potential.