Living in extreme environments, marine organisms face constant exposure to a range of stressors, such as high radiation levels, fluctuations in temperature, and oxidative stress. Understanding extremophile fishes is crucial because it gives us valuable insights into the biochemical, physiological, and developmental processes that govern life, by observing how they operate under natural stressors. Among the most fascinating adaptations is the existence of specialised enzymes and compounds that function as potent antioxidants, successfully counteracting reactive oxygen species’ deleterious effects. In this review, we analysed the findings from several studies on Antarctic and deep-sea fish species, while highlighting the environmental stressors effects toward the antioxidant system. The antioxidant defences of the considered extremophile fishes have been extensively studied, but there is still much to learn to fully understand this complex system, while the relative research is still ongoing. Consequently, we are properly anticipating further advancements over the next few years about our understanding of crucial physiological processes that support cell survival.