The process of preparing extracts for pharmaceutical industry from natural resources is a challenge to obtain effective constituents besides using resources efficiently considering public health and environment. Advanced extraction technologies aim to provide high efficiency and selectivity apart from decreasing the demand for organic solvents causing toxic residuals. In line with this objective, optimization of subcritical water extraction of Morus nigra L. fruits had been carried out with response surface methodology. Bioactive constituents as phenolics, flavonoids and anthocyanins were determined with spectrophotometry and LC MS/MS analysis. Optimum extraction conditions were elicited as 60 degrees C, 60 min, 2 ml/min yielding an IC50 value of 1.84 mg/ml and subcritical conditions at 120 degrees C, 60 min, 2ml/min yielding 1.71 mg/ml which possess stronger activity than extracts of conventional solvent extraction (2.81 mg/ml) regarding tyrosinase inhibitory activity. Consequently, subcritical water could be a pioneer for green extraction systems for Moms nigra L. fruits compared to conventional solvent extraction. (C) 2017 Published by Elsevier B.V.