IntroductionThe species Lantana camara is used in folk medicine. The biological activities of this medicinal plant are attributable to the presence of various derivatives of triterpenoids and phenolic compounds present in its preparations, indicating excellent economic potential.ObjectiveIn this study, the operational conditions of ultrasound‐assisted extraction (UAE) and microwave‐assisted extraction (MAE) were optimized using Box–Behnken design to improve the total phenolic content (TPC) recovered in hydroethanolic extracts of L. camara leaves.Material and methodsThe TPC, total flavonoid content (TFC), and antioxidant activities of the hydroalcoholic extracts of L. camara, prepared by UAE and MAE under the optimized extraction conditions, were compared with those of the extracts obtained by conventional extraction methods.ResultsUnder the optimal conditions, the extracts obtained by UAE (35% ethanol, 25 min, and a solvent‐to‐solid ratio of 60:1 mL/g) and by MAE (53% ethanol, 15 min, and 300 W) provided high yields of 32.50% and 38.61% and TPC values of 102.89 and 109.83 mg GAE/g DW, respectively. The MAE extract showed the best results with respect to TPC, TFC, and antioxidant activities, followed by extracts obtained by UAE, Soxhlet extraction, decoction, maceration, and infusion, in that order.ConclusionThe results obtained indicate that L. camara may be used as an important source of antioxidant phenolic compounds to obtain products with high biological and economic potential, especially when the extraction process is performed under appropriate conditions using MAE and/or UAE, employing environmentally friendly solvents such as water and ethanol.