ABSTRACTInclusion complexation, hydrogen bonds, π–π interaction, dipole–dipole interaction, and steric hindrance effect all contribute to the enantioseparation ability of cyclodextrin (CD) or CD derivatives. In this work, one native cationic CD chiral stationary phases (SHCDCSP) and four derivatized CD‐CSPs, namely, per(4‐trifluoromethyl) phenylcarbamoylated‐β‐CD CSP (SFPhCDCSP), per(4‐chloro) phenylcarbamoylated‐β‐CD CSP (SCPhCDCSP), per(4‐bromo) phenylcarbamoylated‐β‐CD CSP (SBPhCDCSP), and per(4‐methyl) phenylcarbamoylated‐β‐CD CSP (SMPhCDCSP), were prepared via thioether linkage and applied for the enantioseparation of chiral lactides and chiral diketones in both reverse phase (RP) and normal phase (NP) modes. Most of the studied chiral lactides were found to be well resolved (Rs > 1.5) under RP mode, especially Met‐Sty‐Ibn (compound 11) is observed to display highest resolutions (Rs = 5.09, Rs = 3.17) among all the analytes on the SFPhCDCSP and SMPhCDCSP. In NP mode, SFPhCDCSP showed excellent chiral recognition ability towards chiral lactides. The comparison study of CD‐CSPs reveals the structure of CSPs play a significant role on the enantioselectivities.