Insulin resistance is an important feature of metabolic syndrome such as type 2 diabetes and obesity.The underlying mechanisms of insulin resistance are still unclear.Mitochondrial dysfunction, including mitochondrial loss and over-production of oxidants, has been suggested to be involved in insulin resistance.Increasing evidence suggests that targeting mitochondria to protect mitochondria function could prevent and ameliorate various disorders and diseases.In this presentation, I will summarize our recent studies on targeting mitochondria by regulating mitochondrial homeostasis to improve mitochondrial function and Keap1/Nrf2 system to control redox balance for preventing obesity and ameliorating obesity-related disorders.We have focused on natural compounds from traditional Chinese medicine and food including bitter gourd and pomegranate in cellular systems and in animal models of obesity.The in vitro and in vivo studies on the effects and mechanisms of mitochondrial targeting natural extracts or active components, may help us to understand the importance and mechanisms of mitochondrial metabolism, and to find and develop mitochondria-targeting agents from traditional Chinese medicine and food.