Reactive oxygen species (ROS) are major sources of oxidative stress playing prominent roles in the development of several pathologies including cardiovascular and neurodegenerative diseases or cancers. The presence of transition biometal ions, specifically copper and iron, induces ROS formation by catalyzing the reduction of molecular oxygen to superoxide anion (O2˙-), hydrogen peroxide (H2O2) and hydroxyl (HO˙) radical. To limit ROS production and their detrimental effects, we report on the synthesis, physicochemical studies and antioxidant assays of an innovative series of synthetic pentapeptides exhibiting a dual direct/indirect mode of action, both as iron(iii)-chelators and as radical scavengers. These combined effects lead to a drastic reduction of in vitro reactive oxygen species production up to 95% for the more reactive hydroxyl radical.