Medium-chain triglycerides (MCTs) are triglycerides containing medium-chain fatty acids, which have chain lengths of 6–12 carbon atoms. MCTs have been widely used in different diets as a healthy replacement of long chain fatty acids and combined with medications to treat digestive diseases. However, limited study has focused on the effect of MCTs on obese type 2 diabetes mellitus (T2DM) and its complications, including non-alcoholic fatty liver disease (NAFLD) and cardiovascular disorders. It has been reported that MCT based diets can effectively attenuate the progression of NAFLD and improve cardiovascular functions. It remains unclear whether MCT diet can demonstrate similar positive effects on liver and heart under diabetic conditions. To determine the side effects and therapeutic effects, both wild type and diabetic mice were treated with normal chow, MCT based diet and high fat diet (HFD). 8-week-old male WT mice under normal diet and MCT diet for 12 weeks showed similar body weight, glucose tolerance, electrocardiogram, liver triglyceride content and hormone profiles, including insulin and growth hormone, while mice under HFD showed deterioration in those parameters. While showing increased energy intake under both HFD and MCT based diet group, only MCT group showed increased energy expenditure and maintained total energy balance. Following the WT experiments, 10 week-old melanocortin 4 receptor knockout (MC4RKO) mice, an obese mice model due to hyperphagia, were under HFD for 6 weeks to induce T2DM and switched to pair feeding with the same energy intake from normal, MCT diet and HFD for 6 weeks. MCT diet group showed improved glucose tolerance, insulin sensitivity, and reduced liver triglyceride content among all groups. Our study demonstrated that MCT diet has no significant side effect for normal mice and sustained healthy metabolic profiles. MCT diet may have potential positive effects on liver and cardiac function under T2DM.