An efficient ultrasonic-assisted extraction using ultrasonic probe system (UPAE) was developed for the extraction of wedelolactone (WEL) and antioxidant polyphenols from Eclipta prostrate. A central composite design and response surface methodology (RSM) were used to optimize the UPAE. The key parameters considered for the UPAE included solvent type, temperature, ultrasonic power, solvent to material ratio and extraction time. The dependent variables included the yield of WEL, total phenolic content (TPC) and scavenging activity of DPPH radical. For simultaneously maximizing the three responses, the optimal conditions were 48% ethanol-water mixture as solvent, temperature of 40 degrees C, ultrasonic power of 90 W, solvent to material ratio of 50 mL/g and extraction time of 11 min. The predicted values from the developed quadratic polynomial equations were in close agreement with the actual experimental values. The TPC and %DPPH of the optimized UPAE were significantly higher than those of ultrasonic-assisted extraction using ultrasonic bath, heat reflux extraction and Soxhlet extraction. Compared to conventional extraction methods, UPAE provided higher extraction efficiency and offered many advantages such as reduction of time and energy for extraction. The developed UPAE appears to be a green method and have great potential for the extraction of active components and antioxidants from natural products. (C) 2014 Elsevier B.V. All rights reserved.