Aging is a process characterized by a general decline in physiological functions. The high bioavailability of reactive oxygen species (ROS) plays an important role in the aging rate. Red blood cell deformability is the ability of cells to modulate their shape to ensure transit through narrow capillaries of the microcirculation. A loss of deformability can occur in several pathological conditions, during natural aging through an increase in membrane protein phosphorylation, and/or through the structural rearrangements of cytoskeletal proteins due to oxidative conditions, with a key role played by band 3. Due to the close relationship between aging and oxidative stress (OS), functional foods rich in flavonoids are excellent candidates to counteract age-related changes. This study aimed to verify the protective role of Açaì extract in a D-Galactose (D-Gal)-induced model of aging in human red blood cells. Our results showed that Açaì berry extract (10 μg/mL) avoided the formation of leptocytes, prevented the increased OS, and restored alterations in the distribution of band 3 protein (B3p) and CD47 proteins in red blood cells exposed to 100 mM D-Gal. Moreover, the significant decrease in membrane red blood cell deformability associated with D-Gal treatment was alleviated by pre-treatment with Açaì extract. The extract completely restored the increase in B3p phosphorylation and Syk kinase levels, but this effect was only partial for the alterations in the distribution of spectrin, ankyrin, and protein 4.1 after exposure to 100 mM D-Gal treatment. Interestingly, D-Gal exposure was also associated with an acceleration of the rate constant of SO42- uptake through B3p, as well as A1c formation. Both alterations were attenuated by pre-treatment with the Açaì extract. These findings contribute to clarifying the aging mechanisms in human red blood cells and to proposing flavonoid-rich functional foods as natural antioxidants for the treatment and prevention of OS-related disease conditions.