Schefflera octophylla (Lour.) Harms, a kind of traditional Chinese medicine (TCM), is commonly used for anti-inflammatory, analgesic, rheumatism, fever, and hemostasis therapy. In our previous studies, two major triterpenoids were isolated and identified from leaves of S. octophylla, and evaluated for their inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide production in RAW264.7 cells; both of them displayed significant anti-inflammatory activities at their noncytotoxic concentrations. Therefore, it is very useful to establish an efficient and green extraction method to isolated the two major triterpenoids from leaves of S. octophylla. In this paper, ionic liquid based ultrasonic-assisted extraction (ILUAE) was successfully applied to extract the two major triterpenoids from leaves of S. octophylla. Four single factors (ionic liquids (ILs) concentration, solid–liquid ratio, centrifugal speed, mesh number), with a greater impact on extraction rate, were selected from a variety of influencing factors, and the optimal conditions were obtained by Box–Behnken response surface methodology (RSM). Under optimal conditions, the total extraction yield and extraction rate of two triterpenoids were 288.03 mg/g and 28.80%, respectively, which was 6.80% higher than that of 70% Ethanol (220 mg/g and 22%, respectively).