The enantiomers of five profen drugs were simultaneously separated by MEKC with the combined use of 2,3,6-tri-O-methyl-beta-cyclodextrin and chiral cationic ionic liquid, N-undecenoxy-carbonyl-L-leucinol bromide, which formed micelles in aqueous buffers. Enantioseparations of these profen drugs were optimized by varying the chain length and concentration of the IL surfactant using a standard recipe containing 35 mM 2,3,6-tri-O-methyl-beta-cyclodextrin, 5 mM sodium acetate at pH 5.0. The batch-to-batch reproducibility of N-undecenoxy-carbonyl-L-leucinol bromide was tested and found to have no significant impact in terms of enantiomeric resolution, efficiency, and migration time. Finally, this method was successfully applied for the quantitative determination of ibuprofen in pharmaceutical tablets.