Background: The extraction method of bioactive compounds is an important step in the manufacturing of herbal medicines, because secondary metabolites with therapeutic potential are usually found in small quantities in plant materials. Objective: Due the potential of Apeiba tibourbou Aubl, this study aimed to evaluate the impact of the extraction method on the quality of herbal extract and optimize the extraction of fatty acid, rosmarinic (Ra) and caffeic (Ca) acid from A. tibourbou. Materials and Methods: Determinations of residual moisture (Rm), proteins (Pt), lipids (Lp), total fiber (Tf), and carbohydrate (Cy) were performed in triplicate samples according assessment of antioxidant capacity. Extraction of fatty acids was carried out by two different methods: (i) By shoxlet and (ii) bligh and dyer. The optimized conditions were determined by surface response methodology (RSM), and the criterion of desirability was the maximum extraction of Ra and Ca. Results: The method of bligh and dyer was able to extraction more total Lp than the shoxlet. However, the extraction of fatty acid was different for the two methods. The optimized conditions to extract RA and Ca was calculated by RSM, 42°C, 30% (alcohol degree) and 24 min, this conditions maximize simultaneously the extraction of Ca (0, 04%) and Ry (1.89), Conclusion: It was observed that the extraction method alters the chemical composition of extract, and it is possible to extract Ca and Ra from A. tibourbou's leaves using ultrasound-assisted extraction.