According to the free radical theory of aging, accumulation of reactive oxygen species (ROS) within mitochondria throughout lifespan leads to impairment of the main biological macromolecules as DNA, lipids and proteins, which might be at the basis of premature aging. One way to test experimentally such a hypothesis consists in intervention studies using antioxidant nutrients aimed at limiting or inhibiting ROS production that should be able to reduce the aging rate and disease pathogenesis. Grape seed flour (GSF) contains high level of phytochemicals among which bioactive polyphenols exhibit numerous biological properties and beneficial health effects as antioxidant, anti-inflammatory, anti-carcinogenic, multi-organ (heart, liver, kidney, and brain among others) protective. The present study aimed at testing the ability of high dosing GSF (4 g/kg bw) used as a nutritional supplement to slow down aging and prolong lifespan of Wistar rats when administered from early life (one month-old animals) till their natural death. Data clearly show that high dose GSF extends organism longevity and healthspan by improving multi-organ damages, systemic fuelling metabolism declines, and alleviated oxidative stress and inflammation in aging rats. Our data support the extending longevity effect of grape polyphenols especially when used as high dosing nutritional supplement or as natural medicine whose appropriate galenic form as solid lipid nanoformulation, is currently under investigation.