Supercritical carbon dioxide in combination with hydrothermal process was used in the extraction of bioactive compounds from Garcinia mangostana pericarp. The extraction was carried out following pre-defined ranges of temperature (120-160 degrees C), pressure (5-15 MPa), extraction time (30-120min), and particle size (0.3-0.9 mm), that served as parameters for determination of optimum yield. The extracts were subsequently analyzed for their total polyphenolic contents, antioxidant activity, and alpha-mangostin recovery. The multi-variable extraction process yielded several possible responses. Using response surface methodology (RSM) with central composite design (CCD), the optimal response obtained a yield of 39.9% w/w, with 22.0 g(GAE)/100 g(extract) of total polyphenolic contents, together with 73.2 mu g/mL of antioxidant activity and 0.203% w/w(extract) recovery of alpha-mangostin. (C) 2015 Elsevier B.V. All rights reserved.