AbstractPermethylated β‐cyclodextrin (hereafter designated perMe‐β‐CD), dililuted or not in polysiloxane, is an efficient chiral discriminant for native, 3‐methylated, and 1,3‐dimethylated series of 5‐methyl‐5‐(CnH2n + 1)hydantoins. From thermodynamic data obtained with pure perMe‐β‐CD and with the aid of molecular modeling, it is concluded that: (i) For native hydantoin derivatives having a carbon chain at the 5‐position varying from ethyl to nonyl (2⩽n⩽9), the retention time is related to their H‐bonding capability. The resolution is poor for derivatives with n⩽4. For n⩽5, the resolution is considerably improved and this increase in resolution is attributed to the long alkyl chain being capable of being buried inside the cyclodextrin cavity. (ii) For 1,3‐dimethylhydantion derivatives having a carbon chain at the 5‐position varying from ethyl to hexyl(2⩽n⩽6), the retention time is mainly determined by a steric fit between the solute and the inner volume of the macrocyclic cavity. For n = 2, a particular behavior is observed, consistent with a total inclusion of the solutes inside the cavity. By contrast with the native hydantoins, the selectively is high for light derivatives. Thus, the selectivity does not correlate with a strong docking energy (such as the presence of H‐bonds postulated with native derivatives). (iii) For 3‐methylhydantoin derivatives having a carbon chain at the 5‐position varying from ethyl to octyl (2⩽n⩽8), as expected, retension time and selectivity are intermediate between that of native hydantoins and 1,3‐dimethylhydantoins. For all three series, where n⩽5, the increase in chain length (n) does not bring about substantial changes in the chromatographic results. Therefore, for these long alkyl chain derivatives, simi