Flavonoids are a group of plant polyphenol secondary metabolites, which widely exist in plant systems. Recently, flavonoids from plant-based sources have been gaining more interest due to their versatile biological activities. The biological activities of flavonoids are dependent upon their chemical structures, which in turn rely on their structural class, level of hydroxylation, substitution pattern, connection position, existence of C2=C3 double bond, and level of polymerization. Flavonoids are considered nutraceuticals in diet. They help prevent many chronic and degenerative illnesses through various biological activities, such as free radical scavenging, anti-lipid peroxidation, and xanthine oxidase inhibition, as well as their anti-inflammatory, antimicrobial, and anti-cancer activities. The goal of the present review is to evaluate flavonoids’ chemical structural features and their biological activities as they relate to preventing chronic diseases affecting human health, and further navigate the relationship between the chemical structure and their biological function.