By-products of raspberry seeds fruit processing industry are rich in bioactive compounds. Ellagic acid (EA) is a polyphenol naturally present in raspberry seeds which has antioxidant, hepatoprotective, antimicrobial, anti-carcinogenic, anti-inflammatory activity, among other interesting bioactivities. EA majority is bonded in the form of ellagitannins (ETs) which have lower bioactivity when comparing to EA. Hence, ETs have to be hydrolysed to EA. Classical acid hydrolysis of ETs requires utilization of mineral acids (e.g. HCl) and alcohol (e.g. MeOH) which are detrimental for human health and hazardous for the environment. Natural Deep Eutectic Systems (NADES) composed of e.g. citric acid and betaine could serve as alternative medium for the hydrolysis process. This would allow to production edible, non-toxic and ready-to-use extracts which could be further used in food and cosmetic industry. Hydrolysis of ETs to EA using NADES is determined by numerous parameters (e.g. temperature, time, molar ratio of citric acid and betaine in NADES, water content in NADES, NADES/plant ratio etc.) and process optimization with all variables could be time consuming, inefficient and expensive. Thus, it is necessary to reduce their number and determine the most influential variables prior to final optimization step. For that purpose, 25-1 factorial experimental design was applied with a total of 16 experimental setups. The obtained extracts were analysed in terms of EA content which was determined by HPLC method, total polyphenol content analysed with Folin-Ciocalteu procedure and in vitro antioxidant activity determined by DPPH assay. Among all selected variables, NADES/plant ratio, temperature, and time, exhibited the highest impact on EA content, thus, these parameters should be selected for the final optimization step.