Natural Deep Eutectic Solvents (NADESs) are a form of green solvents used to extract phenolic compounds and are considered a more environmentally friendly alternative to traditional solvents. The study aimed to explore a more eco-friendly and effective approach to extracting anthocyanins from Prunus domestica by utilizing NADESs. Four NADESs were created by making combinations of choline chloride with citric acid, lactic acid, glycerol, and ethylene glycol. The study investigated the anthocyanins profile, antioxidant, and anti-sickling properties of fruit extracts that were obtained using NADESs. The examination of NADESs revealed that the hydrogen bond acceptors and donors had a substantial impact on the viscosity, pH, density, and chemical structure of the NADESs. The resulting extracts demonstrated the highest recovery rates, resulting in the greatest total phenolic content (35.05 ± 0.15 mg GAE/100 g) and total anthocyanin content (17.22 ± 0.296 mg CGE/100 g). This extract from the Prunus domestica fruit, which contains anthocyanin, has anti-sickling effects on sickle cell erythrocytes. The Emmel test was used to assess the in vitro anti-sickling effects of the NADES extract. The percent sickling of negative control was found to be 40.88%. And it was discovered that the NADES extract of CHCL: ETHGly was 14.71% at an effective concentration of 0.2% (v/v), and the NADES extract of CHCl: GLY was discovered to be 20.94% at an effective concentration of 0.2% (v/v). The phenolic (anthocyanin) impact on percent sickling revealed a significant difference between the control and test.