Manganese superoxide dismutase (MnSOD) is a vital mitochondrial antioxidant enzyme that preserves cellular integrity by catalyzing the dismutation of superoxide radicals into hydrogen peroxide. Its central role in maintaining redox homeostasis has positioned it as a key target in biomedical research. This review provides an in-depth examination of MnSOD’s structural and functional properties, regulatory mechanisms, and its involvement in the pathogenesis of various human diseases.

Reactive oxygen species (ROS) are double-edged swords in biological systems—they are essential for normal cellular functions but can cause damage when accumulated due to oxidative stress. Manganese superoxide dismutase (MnSOD), located in the mitochondrial matrix, is a key enzyme that neutralizes superoxide radicals (O₂^•−), maintaining cellular redox balance and integrity. This review examines the development and therapeutic potential of MnSOD mimetics—synthetic compounds designed to replicate MnSOD’s antioxidant activity. We focus on five main types: Mn porphyrins, Mn salens, MitoQ10, nitroxides, and mangafodipir. These mimetics have shown promise in treating a range of oxidative stress-related conditions, including cardiovascular diseases, neurodegenerative disorders, cancer, and metabolic syndromes. By emulating natural antioxidant defenses, MnSOD mimetics offer innovative strategies to combat diseases linked to mitochondrial dysfunction and ROS accumulation. Future research should aim to optimize these compounds for better stability, bioavailability, and safety, paving the way for their translation into effective clinical therapies.