The ultrasound-assisted aqueous extraction of polyphenols from Psidium guajava leaves was investigated using response surface methodology. The total polyphenols yield was significantly affected by the process parameters (ultrasonic power, extraction time, and temperature) and the experimental polyphenols yield at optimal conditions (390.68 W, 38.38 min, 63.23 degrees C) was well agreed with the predicted value (59.82 mg GAE/g). Meanwhile, the aqueous extracts had strong scavenging activity to DPPH. The HPLC analysis showed that gallic acid was the main phenolic component in guava leaves. It was also found that this ultrasound procedure could be successfully applied in industrial production.