Christia vespertilionis is a medicinal herb traditionally used as a complementary and alternative medicine to treat cancer and malaria. This study investigated the effect of pre-treatments of the Christia vespertilionis plant on supercritical CO2 extraction yield and solubility. Four pre-treatments were studied: drying and grinding, doping with absolute ethanol (99%) and 80% (v/v) of ethanol/water, and microwave pre-treatment. The supercritical CO2 extraction was conducted at a constant 13.8 MPa, 40℃ with 24 mL/min flow rate in 40 min of extraction time. It was found that the dried sample after drying and grinding pre-treatment produced the highest yield of 4.56 mg/g, whereas the lowest yield was obtained for the fresh leaves’ samples treated with microwave irradiation (1.26 mg/g). Doping techniques with absolute ethanol and 80% (v/v) were comparable in the 2.64 to 2.94 mg/g. GCMS results revealed that Christia vespertilionis extract comprises antioxidants, mainly phytol, limonene, and other medicinal compounds such as α-monolaurin and l-ascorbyl 2,6-dipalmitate. This study indicates that adding co-solvent was not the primary technique in supercritical CO2 extraction to increase the extractability of compounds of interest from plant matrices.