The carcinogenic effects of synthetic antioxidants in foods have led to increased interest in natural sources of antioxidants. Food industries produce substantial quantities of phenolics-rich by-products, which have gained much attention due to their antioxidant properties. Ultrasound assisted extraction (UAE) was applied for the extraction of polyphenol and antioxidants from pomegranate (Punica granatum L.) peel using ethanol-water mixture as a food grade solvent. A central composite design (CCD) and response surface methodology (RSM) were used to optimize experimental conditions for extraction of polyphenol and antioxidants. The independent processing variables were solvent type, solvent to solid ratio, particle size, ethanol concentration (% v:v), temperature (degrees C) and time (min). The dependent variables were total phenolic content (TPC), ferric reducing antioxidant power (FRAP), scavenging activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and yield. TPC varied from 5506.42 to 8923.24 mg gallic acid equivalent/100 g of dry weight. FRAP and DPPH values varied from 24.30 to 63.37 mmol Fe2+/100 g dry weight and 60.12-83.52% inhibition, respectively. Extraction yields ranged from 29.78% to 45.38%. The extract can be used as substitute of synthetic antioxidants for food products, color and oxidative stabilization. Therefore, the highest yield is recommended for industrial applications. The optimal conditions for this aim were 70% ethanol-water mixture as solvent, temperature of 60 degrees C and extraction time of 30 min. The experimental values agreed with those predicted by RSM models, thus indicating suitability of the model employed and the success of RSM in optimizing the extraction conditions. (c) 2012 Elsevier B.V. All rights reserved.