Different extraction conditions may significantly influence extraction of particular compound groups. In the present study, response surface methodology (RSM) based on Box–Behnken design was used to define the best combination of extraction temperature (20–60 °C), ethanol concentration (10–90 %) and extraction time (60–180 min) for maximum yield of antioxidant compounds and maximum antioxidant activity of orange extracts. Experimental values of total phenol yields were in the range from 3.10 to 3.72 mgGAE/ml, while total flavonoid content was in the range from 1.42 to 2.13 mgRE/ml. Antioxidant activity expressed as the 50 % inhibition concentration (IC50 value) was in the range from 0.03 to 0.04 mg/ml. The experimental results were fitted to a second-order quadratic polynomial model, and they have shown a good fit to the proposed model (R2 > 0.90). Determined optimized conditions for maximizing yield of antioxidant compounds were within the experimental range.