Yerba mate (Ilex paraguariensis A.St-Hil.) is an autochthonous plant species from South America whose leaves exhibit beneficial health properties due to the presence of alkaloids and antioxidants. In the present study, the content of alkaloids and antioxidants in yerba mate extracts obtained by supercritical CO2 extraction was analyzed. Extractions were carried out using ethanol and hydrated ethanol as co-solvents at up to 333 K and 26.0 MPa. Bioactive extracts with a high concentration and yield of alkaloids (11.9 wt% and 5.0 g kg−1 of yerba mate, respectively) were obtained when pure ethanol was used as co-solvent. The alkaloid selectivity decreased and the antioxidants extraction capacity increased to a maximum of 8.4 g kg−1 of yerba mate when hydrated ethanol was loaded as co-solvent. Thus, by controlling the solvent composition and the extraction conditions, extracts rich in alkaloids or antioxidants can be obtained for the development of nutraceutical and functional food products.