Complex stability constant (K), standard free energy (DeltaGdegrees), reaction enthalpy (DeltaHdegrees), and entropy change (TDeltaSdegrees) for 1:1 inclusion complexation of the diastereomeric dipeptides Z-D/L-Glu-L-Tyr (Z = benzyloxycarbonyl) and its component amino acids (Z-D/L-Glu and N-Ac-Tyr) with native alpha-, beta-, and gamma-cyclodextrins (CDs) and A,X-modified bis(6-trimethylammonio-6-deoxy)-beta-CDs (AX-TMA(2)-beta-CDs) were determined in buffer solution (pH 6.9) at T = 298.15 K by isothermal titration microcalorimetry. Concurrent NMR spectral examinations revealed that the penetration mode and the resulting complex architecture are dramatically altered by the peripheral modification and also by the CD's cavity size. Upon complexation of the ditopic Z-Glu-Tyr guest, native alpha- and beta-CDs preferentially bind the Z's phenyl group, whereas AX-TMA(2)-beta-CDs predominantly include the Tyr's phenol moiety. In contrast, native gamma-CD includes both of the aromatic moieties simultaneously in the same cavity. Furthermore, for isomeric AB-, AC, and AD-TMA(2)-beta-CDs, an inversion of enantioselectivity and a switching of the penetration mode were observed, critically depending on the position of TMA substituents.