Background: Several ethnobotanical and ethnopharmacological studies have shown the therapeutic potential of plants from the genus Tabebuia, which have long been used in traditional medicine in rural areas of South America, for the treatment of several human diseases. This study aimed to evaluate the Nrf2-mediated antioxidant activity of the inner bark extracts obtained from Tabebuia rosea and Tabebuia chrysantha. Methods: The antioxidant activity of extracts obtained from the inner bark of T. rosea and T. chrysantha was evaluated using the Oxygen radical absorbance capacity (ORAC) technique. The effect of extracts on the viability of HepG2 cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. The translocation of Nrf2 to the nucleus after exposure of HepG2 cells to the extracts and controls (α-lipoic acid, curcumin and hydrogen peroxide) was evaluated using the Nrf2 transcription factor kit. Induction of the Nrf2-mediated antioxidant response gene ( NQO1) was evaluated by real-time PCR. Results: The ethyl acetate extract obtained from both species displayed the highest ORAC activity (12,523 and 6,325 µmoles Eq Trolox/g extract). In addition, the extracts had the ability to activate and to translocate Nrf2 to the nucleus, as well as to induce the expression of NQO1. Conclusion: These results indicate that the ethyl acetate extracts obtained from the inner bark of T. chrysantha and T. rosea have an important antioxidant effect mediated by Nrf2 activation, and could be used as a new source of natural antioxidants.