Abstract: Mitochondrion is one of the most vital organelles in cells of human body, and it is involved in many metabolic processes. Mitochondrion dysfunction is closely related to many diseases such as cancers, neurodegenerative diseases, obesity and ischemia reperfusion injury. As a result, mitochondrial drug delivery has gained more and more attention in the drug discovery against these diseases. This review gives a brief introduction to the relationship between mitochondria and human diseases (e.g., cancer), and summarizes the latest trend of mitochondrial targeting drug delivery system (MTDDS).