Phaleria macrocarpa, one of many indigenous Indonesian plants, possesses potent antioxidant activity and hence may serve as natural food preservative, cosmetic ingredients, as well as food supplement. This study is the second stage of a three-year project to isolate antioxidant components in Phaleria macrocarpa for natural preservative application. The objective of this study is to investigate the effect of pretreatment process on the oleoresin and bioactive content, and to optimize three parameters in the extraction process, i.e. ethanol concentration, F/S ratio, and temperature. The selected pretreatment method was solid-liquid extraction using a non-polar solvent (n-hexane) and a semi polar solvent (ethyl acetate). The pretreatment process produced less sticky oleoresin, especially with n-hexane, due to significant removal of tannin, and had only a little effect (less than 4%) on the antioxidant activity and flavonoid content. However, the pretreatment indeed reduced the yield of oleoresin by around 10%. Three important parameters of the extraction process were optimized using Central Composite Experimental Design by varying operation temperature from 27.5 °C to 64.5 °C, F/S ratio from 1 : 11.5 g/mL to 1 : 53.5 g/mL, and ethanol concentration from 14 %-v/v to 93 %-v/v. The response surface analysis showed a maximum point at ethanol concentration of 30 %-v/v, F/S ratio of 1 : 45 g/mL, and temperature at 57 ºC which gave the oleoresin yield of 1.00 g oleoresin/g dry feed and antioxidant activities of 2.99 μmol DPPH/mg oleoresin.