ArtículoAbstract A Box–Behnken design (Extraction-time, pulsecycle, sonication-amplitude) was employed to extract phenolic compounds from Justicia spicigera leaves by ultrasonic-assisted extraction. The muicle leaves extracts were analyzed measuring total phenolic compounds and antioxidant capacity. According to response surface methodology the optimal conditions of ultrasonic-assisted extraction to obtain the highest soluble phenolic content were 2 min (extraction time) for 0.7 s (pulse cycle) at 55% of sonication amplitude. Under these optimal conditions, the total phenolic content was higher when was used ultrasonic-assisted extraction (54.02 mg/g) than stirring (46.46 mg/g) and thermal decoction (47.76 mg/g); however, the antioxidant capacity from J. spicigera extracts did not increase by ultrasonic-assisted extraction. The extracts or aqueous infusions from J. spicigera leaves are used for therapeutic proposes, therefore the ultrasonic-assisted extraction is a useful technology to improve the extraction of phytochemicals from J. spicigera leaves.