This study aimed to investigate the cytoprotective effects of flavonoids, their metabolites alone or in combination against hypoxia/reoxygenation induced oxidative stress in the transformed human first trimester trophoblast cell line (HTR-8/SVneo). Oxidative stress was achieved with hypoxia followed by reoxygenation and the following assays were performed: MTT, CellTox ™ Green Cytotoxicity, CellTiter-Glo ® , NADP/NADPH-Glo™, ROS-Glo™/H2O2, GSH/GSSG-Glo™ and Caspase-Glo ® 3/7 assays. HTR-8/SVneo cells, pre-treated for 24 h with flavonoids or their metabolites were protected significantly from oxidative stress. Flavonoids were associated with ROS modulation, reducing the generation of superoxide/hydrogen peroxide. The activities of caspases 3/7 were also significantly reduced significantly in HTR-8/SVneo cells pre-treated with flavonoids. This study has shown for the first time that 24 h pre-treatment with flavonoids, their metabolites alone or in combination, protected against HRinduced oxidative stress in the trophoblast cell line. These data indicate that dietary flavonoids may be beneficial to placental health and invasion during early gestation.