This work examined the efficacy of Natural Deep Eutectic Solvents (NADES), consisting of choline chloride, betaine, and L-carnitine as hydrogen bond donors (HBD) and various acids (citric, malic, lactic, tartaric, and oxalic acids) as hydrogen bond acceptors (HBA), for the extraction of gingerols and shogaol using the computational model COSMO-RS and validated the findings experimentally. The Conductor-like Screening Model for Real Solvents (COSMO-RS) results indicate that five combinations of NADES were anticipated to strongly attract gingerols and shogaol. ChCl: MaA (1:1), ChCl: LaA (1:1), Be: MaA (1:1), Be: LaA (1:2), and Be: OxA (1:1). Laboratory investigations demonstrated that gingerols had a strong affinity for ChCl: LaA (1:1), Be: CiA (1:2), Be: MaA (1:1), Be: LaA (1:2), and Be: TaA (1:1). The COSMO-RS model serves as an excellent tool for determining suitable NADES for dissolving red ginger compounds and may also facilitate the speedy and efficient screening of possible candidates. Our research shows that Be: LaA (1:2) functions as a NADES for the extraction of gingerols from red ginger, yielding a total concentration of 15.0882 mg/g ± 0.062. © The Author(s) 2025.