Recently, research studies on nutraceutically important polyphenolic substances have attracted intensive attention. Berberis vulgaris is an important source of polyphenolic compounds and is often used in traditional medicine. In this study, the extraction of rutin and apigenin rich oil from Berberis vulgaris fruits was evaluated by supercritical carbon dioxide (Sc-CO2) extraction method with and without co-solvent. As valuable antioxidants, rutin and apigenin content of extracts were analyzed by HPLC, and their amounts were maximized via parametric optimization. The rutin compound studied in this research has the potential to be a drug against the COVID-19 virus. The operating conditions were considered in the range of 35-70 degrees C temperatures, 140-240 bar of pressures, 0.35-1.00 mm of mean particle sizes, 3-7 l/min of CO2 flow rates, and 0-8% w/w co-solvent. As a result of Sc-CO2 extractions, the amounts of rutin and apigenin were found as 173 +/- 14.97 mu g/g and 2.91 +/- 0.11 mu g/g, respectively, with the 8% (w/w) co-solvent addition. The amounts of rutin and apigenin obtained by Soxhlet extractions were found as 208.81 +/- 8.48 mu g/g and 6.55 +/- 0.21 mu g/g, respectively. When the Sc-CO2 method was compared with the Soxhlet method, it was seen that the fast and eco-friendly Sc-CO2 method was an ideal extraction method by providing 76.89% rutin and 44.53% apigenin recoveries. As a result of this study, the maximum extraction conditions for rutin and apigenin were obtained as 160 bar, 40 degrees C, 0.35 mm particle size, 3 l/min CO2, 8% w/w co-solvent ratio, and 120 min extraction period.