The increased oxidative stress in the acceleration of the aging process and development of the neuronal disorder are the common feature detected in neurodegenerative illness, such as Alzheimer’s disease, Parkinson’s disease, and Amyotrophic lateral sclerosis. Searching for new treatment against these diseases, the inclusion of exogenous antioxidant agents has shown good results. Flavonoids are polyphenols compounds present in plants, fruits and vegetables that exhibit potent antioxidant and biological properties, which are related to their chemical structure that to confer an excellent radical scavenging ability. The design of metal-flavonoid complexes allows to obtain compounds with improved biological and physicochemical properties, generating important increase of the flavonoid antioxidant properties. This evidence we motive to propose that antioxidant properties of the metal flavonoids compounds can play an important role in the design of potential novel therapeutic strategies. This review presents the structure-activity relationship on the antioxidant properties of three series of metal-flavonoid complexes: M-(quercetin), M-(morin), and M-(rutin). In general, we observed that the coordination sites, the metal ion type used, and the molar ratio metal:flavonoid present in the complexes, are important factors for to increase the antioxidant activity. On these evidences we motive to propose that the development of metal-flavonoid compounds is a potentially viable approach for combating neurodegenerative diseases.