Ischemia-reperfusion (I/R) injury is common during surgery and often results in organ dysfunction. The mechanisms of I/R injury are complex, diverse, and not well understood. RNA methylation is a novel epigenetic modification that is involved in the regulation of various biological processes, such as immunity, response to DNA damage, tumorigenesis, metastasis, stem cell renewal, fat differentiation, circadian rhythms, cell development and differentiation, and cell division. Research on RNA modifications, specifically N6-methyladenosine (m6A), have confirmed that they are involved in the regulation of organ I/R injury. In this review, we summarized current understanding of the regulatory roles and significance of m6A RNA methylation in I/R injury in different organs.