Natural flavonoids as the glycoside forms in vegetables and fruits are the most important phytochemicals in diets. Flavonoid glycosides are hydrolyzed both in the oral cavity and intestine to produce more bioactive and absorbable aglycones, which is meaningful to the health benefits of flavonoids. Here the structure-stability relationship/structure-antioxidant activity relationships of flavonoids were summarized. Although natural flavonoids displayed various bioactivities in cell and animal levels; however, their clinical outcomes are still limited. Isoquercetin, quercetin, EGCG, and genistein are hot molecules in clinical trials. It is really important to carry out large scale clinical and human studies in order to evaluate flavonoids benefits.