Following oxidative stress, modifications of several biologically important macromolecules have been demonstrated. In this study we investigated the effect of a natural extract from Mangifera indica L (Vimang), its main ingredient mangiferin and epigallocatechin gallate (EGCG) on energy metabolism, energy state and malondialdehyde (MDA) production in a red blood cell system. Analysis of MDA, high energy phosphates and ascorbate was carried out by high performance liquid chromatography (HPLC). Under the experimental conditions, concentrations of MDA and ATP catabolites were affected in a dose-dependent way by H 2 O 2 . Incubation with Vimang (0.1, 1, 10, 50 and 100 μg/mL), mangiferin (1, 10, 100 μg/mL) and EGCG (0.01, 0.1, 1, 10 μM) significantly enhances erythrocyte resistance to H 2 O 2 -induced reactive oxygen species production. In particular, we demonstrate the protective activity of these compounds on ATP, GTP and total nucleotides (NT) depletion after H 2 O 2 -induced damage and a reduction of NAD and ADP, which both increase because of the energy consumption following H 2 O 2 addition. Energy charge potential, decreased in H 2 O 2 -treated erythrocytes, was also restored in a dosedependent way by these substances. Their protective effects might be related to the strong free radical scavenging ability described for polyphenols.