Resveratrol (RSV), as a functional food component extracted from natural plants, has been widely studied and recognized in preventing and treating various diseases, with major mechanisms including executing anti-inflammation and anti-oxidation functions, and improving mitochondrial quality. Chronic diseases as non-communicable diseases are mainly caused by multiple factors, such as physiological decline and dysfunction in the body, and have become a significant challenge on public health worldwide. It is worth noting that chronic diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), muscle atrophy, cardiovascular disease, obesity, and cancer are accompanied by abnormal mitochondrial function. Therefore, targeted regulation of mitochondria may be a meaningful way to prevent and treat chronic diseases. Increasing evidence has confirmed that RSV is actively involved in regulating mitochondria, and it has become an essential consideration to prevent and treat chronic diseases through targeting mitochondria and improving corresponding functions. In this article, current studies on RSV to optimize mitochondrial quality for preventing and alleviating chronic disease are systematically summarized, which can provide a theoretical reference for the development of functional foods or drugs to combat chronic diseases.