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Exercise physiology has gained increasing interest due to its wide effects to promote health. Recent years have seen a growth in this research field also due to the finding of several circulating factors that mediate the effects of exercise. These factors, termed exerkines, are metabolites, growth factors, and cytokines secreted by main metabolic organs during exercise to regulate exercise systemic and tissue-specific effects. The metabolic effects of exerkines have been broadly explored and entail a promising target to modulate beneficial effects of exercise in health and disease. However, exerkines also have broad effects to modulate redox signaling and homeostasis in several cellular processes to improve stress response. Since redox biology is central to exercise physiology, this review summarizes current evidence for the cross-talk between redox biology and exerkines actions. The role of exerkines in redox biology entails a response to oxidative stress-induced pathological cues to improve health outcomes and to modulate exercise adaptations that integrate redox signaling.