Chiral differentiation of four enantiomeric pairs of beta-amino acids, cis-(1R,2S)-, cis-(1S,2R)-, trans-(1R,2R)-, and trans-(1S,2S)-2-aminocyclopentanecarboxylic acids (cyclopentane beta-amino acids), and cis-(1R,2S)-, cis-(1S,2R)-, trans-(1R,2R)-, and trans-(1S,2S)-2-aminocyclohexanecarboxylic acids (cyclohexane beta-amino acids) was performed successfully by using host-guest complexes and ion/molecule reactions. The experiments were conducted by using electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. The effect of a chiral host molecule was tested by using three different host compounds; (+)-(18-Crown-6)-2,3,11,12-tetracarboxylic acid, (-)-(18-Crown-6)-2,3,11,12-tetracarboxylic acid, and beta-cyclodextrin. This is the first time that small enantiomeric pairs with two chiral centers have been differentiated using ion/molecule reactions and host-guest complexes.