As one of the most used citrus fruits in the world, orange produces a large amount of waste, mostly in the form of peels. Orange peel represents a large amount of biomass rich in bioactive compounds that could be reused in the food and pharmaceutical industry. According to green chemistry principles, it is essential to invent an extraction process that is economically acceptable and safe for the environment. According to this, deep eutectic solvents have shown to be an excellent substitute to commonly used organic solvents in extractions that are often volatile and harmful to the environment. In this paper, the cytotoxic ability of orange peel extract prepared in choline-chloride:glycerol with different water ratios has been explored, as well as the type of cell death on HeLa and HaCaT cell cultures. The extract prepared in ChClGly with 30 % (v/v) water has shown the strongest antiproliferative effects compared to the ones prepared in buffer solution and ChClGly with 80 % (v/v) water. The effect of the extract in ChClGly with 30 % (v/v) water is dose- and time-dependent, and could be connected with the induction of necrosis in HeLa cells, and apoptosis in HaCaT cells. Extracts prepared in buffer solution and ChClGly with 80 % (v/v) water have shown no significant results. The cytotoxic effect that was stronger on HeLa cells than on HaCaT cells could imply potential antitumor properties of orange peel extract whose biological activity has also been enhanced in natural deep eutectic solvents in comparison to conventional solvents.