Industrial processing of raspberries into juice and jam results in the production of with high content of lipophilic and hydrophilic phytochemicals. Usually considered as waste, raspberry pomace is occasionally cold-pressed to recover specialty oil. However, the resulting pomace press-cake (PPC) still contains 30% to 35% of lipophilic compounds, such as essential fatty acids, tocols, phytosterols, and ellagitannins initially present in pomace. In a perspective of sustainable development, we investigate an eco-friendly process using an aqueous enzyme-assisted extraction (AEAE) to simultaneously and effectively recover lipophilic compounds and polyphenols from the PPC. The performance of different combinations of carbohydrases and proteases was compared. After selecting the best enzymatic system, a definitive screening design involving six factors was then implemented to optimize the process. Under optimized conditions, 1.2 units of thermostable alkaline protease/100 g PPC, pH 9, 60 degrees C, and 2 hr hydrolysis, more than 38% of total PPC lipophilic content were recovered in the aqueous medium. The recovery of polyphenols and antioxidant activity was, respectively, 48% and 25% higher than obtained by extraction with methanol/acetone/water mixture. Such an AEAE extract might prove useful in food and nutraceutical applications. Practical Application Raspberry pomace, a food industrial by-product, is often considered as waste. However, it is a rich source of phytochemicals, such as tocols, polyphenols, and polyunsaturated fatty acids. To overcome the drawbacks of organic solvent use, an enzyme-assisted extraction process was developed as an eco-friendly alternative to recover these bioactive compounds. Definitive screening design experimental design was used to enhance polyphenols and lipophilics extraction yields while reducing process costs. This extract is an oil-in-water emulsion, with high content in antioxidant phytochemicals, which might have potential for use in nutraceutical applications. Therefore, this green process developed for the valorization of raspberry pomace is considered as a perspective of sustainable development.Read less <