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Abstract The enzyme-assisted extraction of bioactive compounds from plants has been studied as an alternative green technology and the carbohydrases have been candidates to improve the extraction process of numerous such compounds from plants. Polyphenols are secondary plant metabolites, generally involved in the defense against different types of stress and yerba mate (Ilex paraguariensis A. St.-Hil., Aquifoliaceae) is a natural source of these antioxidant compounds. The aim of this work was to evaluate the enzyme-assisted extraction of polyphenols from green yerba mate employing response surface methodology (RSM), in order to determine the best extraction conditions. The independent variables were temperature (33.2 to 66.8 °C), enzyme concentration (0 to 336 FGBU/100g), reaction time (19 to 221 minutes) and pH (2.82 to 6.18). The use of carbohydrases increased the extraction of polyphenols from about 38.67% to 52.08%. The present results showed that all the independent variables were significant at the linear level and that temperature and pH were not significant at the quadratic level. The interactions of temperature and pH; enzyme and reaction time; and enzyme and pH were significant. The regression model presented a determination coefficient (R2) close to 0.85 and a fitted value close to 0.45. Considering the results of this study and their industrial viability, the best conditions for the extraction of polyphenols from green yerba mate are a temperature of 50.0 °C, enzyme concentration of 168 FGB/100 g, reaction time of 120 minutes and pH value of 4.50. This study was the first RSM-based report of the optimization of the enzyme-assisted extraction of total phenolic compounds from green yerba mate.