Abstract Polyphenols have been associated with the bioactive potential of grapes due to their beneficial health effects. For this reason, the aim of this study was to determine the content of bioactive compounds and in vitro antioxidant activity of selected Vitis vinifera and Vitis labrusca grapes widely produced in Brazil. In order to evaluate the efficiency of different methods for the extraction of the main polyphenols in grape, four methods were tested and compared. Among the extraction methods evaluated, liquid–liquid extraction was selected as the best method, which showed the best precision and repeatability. The phenolic compounds of white and red V. vinifera and V. labrusca grapes indicated that the type and concentration of polyphenols were mainly dependent on the grape variety rather than the species. The antioxidant activity of all grape samples evaluated was strongly correlated to the trans -resveratrol content (R > 0.9). Among all samples, it was observed that V. labrusca varieties, especially Bordo and Concord grapes widely cultivated in the south of Brazil, presented higher antioxidant potential, associated with the presence of higher content of bioactive compounds.