The goal of this review was to summarize reported studies focusing on cellular reductive stress-induced mitochondrial dysfunction, cardiomyopathy, dithiothreitol- (DTT-) induced reductive stress, and reductive stress-related free radical reactions published in the past five years. Reductive stress is considered to be a double-edged sword in terms of antioxidation and disease induction. As many underlying mechanisms are still unclear, further investigations are obviously warranted. Nonetheless, reductive stress is thought to be caused by elevated levels of cellular reducing power such as NADH, glutathione, and NADPH; and this area of research has attracted increasing attention lately. Albeit, we think there is a need to conduct further studies in identifying more indicators of the risk assessment and prevention of developing heart damage as well as exploring more targets for cardiomyopathy treatment. Hence, it is expected that further investigation of underlying mechanisms of reductive stress-induced mitochondrial dysfunction will provide novel insights into therapeutic approaches for ameliorating reductive stress-induced cardiomyopathy.