The effect of the combined use of amino acid-based ionic liquids (AAILs) and deep eutectic solvents (DESs) with either cyclodextrin-(CD) or cyclofructan-(CF) based chiral selectors for the chiral separa-tion of amphetamine derivatives was investigated in the present study. A non-significant improvement in enantiomeric separation of target analytes was observed when AAILs were combined with either CF or CD. On the other side, a markedly improved chiral separation of enantiomers was obtained using the dual carboxymethyl-& beta;-cyclodextrin/DES system, highlighting the existence of a synergistic effect. After the addition of 0.5% v/v of choline chloride-ethylene glycol, the resolution of the enantiomers of am-phetamine, methamphetamine and 3-fluorethamphetamine, increased from 1.4, 1.1, 1.0 to 1.8, 1.8, and 1.5 min, and the analysis times increased from 19.54, 20.48, 18.71 to 35.71, 35.78 and 32.90 min, re-spectively. This was not the case for the CF/DES dual system, in which the separation of amphetamines worsened, indicating an antagonistic effect. In conclusion, DESs are a very promising additive in capil-lary electrophoresis that can improve the separation of chiral molecules in combination with CDs but not CFs. & COPY; 2023 Elsevier B.V. All rights reserved.