Combined design composed of mixture design and response surface methodology (RSM) was firstly applied for simultaneously optimization of extraction conditions (solvent concentration and ultrasonic conditions) to obtain maximum amount of phenolic compounds from virgin olive oil waste. Various water:methanol (0-1000 mL/L) mixtures were used as solvent under different ultrasonic temperature (30-60 degrees C), amplitude (20-100%) and time (10-30 min) conditions. Phenolic yields of the extracts ranged from 1.6 to 45 mg/g. Generally, increase of time, temperature and amplitude raised extraction yield; however, at elevated temperature and amplitude levels, phenolics were degraded. Optimum ultrasonic condition varied depending on the solvent concentration, that is reason of why combined design is necessary. Optimum water:methanol concentration was 499:511 mL/L; optimum ultrasonic temperature, amplitude and time was 60 degrees C, 13.71% and 21.05 min, respectively. Findings highlighted that combined design has potential to be used in many areas of food industry for optimization of many parameters with low experimental points. (C) 2016 Elsevier Ltd. All rights reserved.