Leucaena leucocephala (Lam.) de Wit seeds, also known as river tamarind, contain sulfhydryl compounds that exhibit antioxidant effects. However, these seeds also possess a toxic effect from mimosine. In this study, the river tamarind seeds were extracted using a natural deep eutectic solvent (NADES) based UAE. Among six NADES compositions screened, choline chloride-glycerol (ChCl-Gly) and choline chloride-sucrose (ChCl-Suc) were selected to be further optimized using a Box-Behnken Design in the RSM. The optimization of total sulfhydryl content was performed in 17 runs using three variables, namely water content in NADES (39%, 41%, and 43%), extraction time (5, 10, and 15 min), and the liquid-solid ratio (3, 5, and 7 mL/g). The highest concentration of sulfhydryls was obtained from ChCl-Gly-UAE (0.89 mg/g sample) under the conditions of a water content in NADES of 41% (v/v) and a liquid-solid ratio …