Purpose: Obesity and diabetes are often accompanied by chronic inflammation and insulin resistance, which lead to complications such as diabetic cardiomyopathy. Ginsenoside Rb1 has been used to treat diabetes and obesity and reduce inflammation as well as risk of heart diseases. However, the role of ginsenoside Rb1 in treating diabetic cardiomyopathy remains unclear. Methods: Diabetic mice were administered ginsenoside Rb1 for 12 weeks, and their body weight, body fat, and blood glucose levels as well as and serum insulin, lipids, and adipocytokine levels were assessed. Lipid accumulation, pathological morphology of the adipose tissue, liver, and heart were examined. Western blot and qRT-PCR were performed to investigate the molecular changes in response to ginsenoside Rb1 treatment. Results: Ginsenoside Rb1 treatment significantly reduced body weight and body fat, attenuated hyperglycemia and hyperlipidemia, and ameliorated insulin resistance and abnormal levels of adipocytokines in diabetic mice. In addition, lipid accumulation and inflammation reduced while the functions of heart improved in the ginsenoside Rb1-treated group. Furthermore, antioxidant function improved in the ginsenoside Rb1-treated diabetic hearts. PCR and Western blotting analyses revealed that the lipid-lowering effect of ginsenoside Rb1 and the resulting improvement of cardiac function could be attributed to the adipocytokine pathway, which promoted energy homeostasis and alleviated cardiac dysfunction. Conclusion: Ginsenoside Rb1 lowered lipid levels in a adipocytokine-mediated manner and attenuated hyperglycemia/hyperlipidemia-induced oxidative stress, hypertrophy, inflammation, fibrosis, and apoptosis in cardiomyocytes.