Mitochondria are the main organelles that produce adenosine 5 ′ -triphosphate (ATP) and reactive oxygen species (ROS) in eukaryotic cells and meanwhile susceptible to oxidative damage. The irreversible oxidative damage in mitochondria has been implicated in various human diseases. Increasing evidence indicates the therapeutic potential of mitochondria-targeted antioxidants (MTAs) for oxidative damage-associated diseases. In this article, we introduce the advantageous properties of MTAs compared with the conventional (nontargeted) ones, review different mitochondria-targeted delivery systems and antioxidants, and summarize their experimental results for various disease treatments in different animal models and clinical trials. The combined evidence demonstrates that mitochondrial redox homeostasis is a potential target for disease treatment. Meanwhile, the limitations and prospects for exploiting MTAs are discussed, which might pave ways for further trial design and drug development.

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