BACKGROUND: Morus nigra (mulberry) fruit has been reported as a source of bioactive compounds, although information about their leaves is very limited. Usually, they are considered wastes and have been traditionally used only for tea preparation. The main objective of this work was to explore the valorization of mulberry leaves by polyphenols microwave-assisted extraction (MAE) and characterization of their antioxidant activity and phenolic composition. A 2(3) factorial design combined with response surface methodology were applied to characterize the effect of main microwave parameters on total phenolic content (TPC). RESULTS: The optimized MAE conditions were 20mL of ethanol:water (1:1; v/v), 120 degrees C, 28 min, 0.414 g and medium stirring speed. Under these conditions, TPC was 19.7 +/- 2.0 mg gallic acid equivalents (GAE) g(-1) dry plant (DP), and antioxidant activity was 15.3 +/- 1.0 mg ascorbic acid (AA) g(-1) DP (ferric reduction activity power -FRAP- assay), 18.6 +/- 1.3 mg Trolox equivalents (TE) g(-1) DP (2,2-diphenyl-1-picrylhydrazyl -DPPH- assay) and 186 +/- 15mg TE g(-1) DP (oxygen radical absorbance capacity -ORAC- assay). When compared with ultrasound extraction and Pharmacopeia reference method, MAE was more efficient, representing a valuable technology. Of the 13 compounds identified by HPLC, the most abundant were rutin, chlorogenic, beta-resorcylic and caffeic acids. CONCLUSION: These results indicate that mulberry leaves are of potential interest for agro-food industries as a new source of natural antioxidants. (C) 2017 Society of Chemical Industry