In the last years, the possibility to exploit the high added value bioactive compounds obtained by the solid residues of the winemaking process in cosmetic, food supply and pharmaceutical field was explored. To enhance the biocompatibility of the final products and reduce the environmental impact of traditional extraction routes, researchers attempted at developing sustainable and green extraction processes. In the present work, the feasibility of employing NaDES (Natural Deep Eutectic Solvents) as a cheap and non-toxic alternative to traditional solvents for the extraction of bioactive compounds from winery wastes of Merlot marc was studied. Furthermore, a two-level factorial design was used to study the single and combined effect of process variables, namely, solid to liquid ratio dry grinding time and extraction time, on the extraction yield. Experimental show that, in the range studied, solid to liquid ratio has a predominant effect and both grinding and extraction times have a slightly appreciable effect on the extraction yield.