Hedyotis corymbosa is a good source of oleanolic acid (OA) and ursolic acid (UA), which have many beneficial effects on human health and are two interesting compounds that are widely utilized in medicine and functional food. To isolate OA and UA from the plant, a novel procedure employing ultrasound-assisted supercritical carbon dioxide (USC-CO2) extraction was developed, and its performance was compared with that of conventional processes. HPLC analysis of the obtained extracts revealed that the highest yields of OA (2.316 mg/g dry plant) and UA (9.284 mg/g dry plant) were achieved by USC-CO2 extraction using a dried sample with a mean particle size of 0.355 mm at a CO2 flow rate of 2.1 mL/min, temperature of 53 degrees C and pressure of 26.5 MPa. The static extraction time was 15 min and the dynamic extraction time was 80 min with 11.0% aqueous ethanol (80% (v/v) ethanol in water) as a cosolvent. The yields obtained with USC-CO2 extraction were higher than those obtained with conventional SC-CO2 extraction and heat-reflux extraction for the two discussed compounds. With the newly developed process, these results were obtained faster and at a lower temperature and pressure; additionally, less organic solvent was used. Therefore, USC-CO2 extraction, as performed under the above-mentioned conditions, is a more effective and selective method for extraction of OA and UA from H. corymbosa compared with the other two techniques. USC-CO2 extraction is efficient and environmentally friendly for using in the pharmaceutical industry. (C) 2015 Elsevier B.V. All rights reserved.