Ischemia-reperfusion is a characteristic disorder of many diseases, such as myocardial infarction, stroke, and peripheral vascular diseases. Ischemia-reperfusion injury (IRI) is one of the most frequent causes of debilitating diseases and death. Relieving organ damage caused by IRI is valuable in safeguarding human life and health. In recent years, nanoplatform-based reactive oxygen species (ROS) scavengers have attracted widespread attention for alleviation of IRI. To highlight these achievements and to provide a quick perspective for researchers to understand the current research status, recent progress in nanoplatform-based ROS scavengers for IRI therapy is summarized in this review. This review first summarizes information on the main sites and mechanisms of IRI. Thereafter, this review briefly summarizes and discusses the principles of design, fabrication, and administration of nanoplatform-based ROS scavengers. Furthermore, the application of nanoplatform-based ROS scavengers in the treatment of IRI in a variety of organs is also reviewed. Finally, limitations and possible breakthrough in developing ROS scavengers in the field of IRI are discussed. It is hoped that this review will be helpful and enlightening to researcher in medicine, pharmacy, biology, chemistry, and materials science.