Manganese-Based Antioxidant Agents: Understanding Structure–Activity Relationships in Biological Applications

Eliminating reactive oxygen species has emerged as an effective therapeutic strategy for diseases related to oxidative stress, such as inflammation, neurodegenerative diseases, and cardiovascular diseases. Manganese (Mn) is an essential component of natural antioxidant enzymes, for example, superoxide dismutase (SOD) and catalase (CAT), thus has been extensively used to design artificial antioxidants. This review provides a systematic summary of how the structural engineering of Mn-based antioxidant agents influences their SOD/CAT-like activity. Critical structural parameters, such as Mn valence states, ligand coordination, codoping with other elements, particle size, and morphology, are discussed to correlate the structure—antioxidant performance relationships. Two major biological functions, including regulating immune cell polarization and protecting cells from oxidative damage, are highlighted. Finally, challenges in this field are outlined, and our perspectives on future research are provided. It is expected that this review will provide insights for the further development of advanced Mn-based antioxidants for biomedical applications.