The paper reported a joined mass spectrometric, crystallographic and quantum chemical study of crystallohydrates, emphasizing on clathrates of native α-, and β-cyclodextrins as well as their randomly acetylated derivatives (4 and 5). The physical data are compared with 19 crystals of CDs, three of which new ones, differed by number of crystallohydrate (and/or clathrate) molecules (n)). The macroscopic complex CDs/n stability (n∈[0.60–12.26]) is evaluated theoretically, accounting the surface and clathrate self-assembly of non-covalent hydrogen bonding interactions. The variety of competitive condensation processes of randomly acetylated products and the non-specific phase transition adduct of CDs and aggregates, which complicated significantly the MS picture are discussed. The single crystal X-ray diffraction, enable to determine the non-covalent interactions in CDs crystals, which physical phenomena in the gas-phase and crystalline phase→liquid phase→GP and CP→GP transitions are evidenced mass spectrometrically. The quantum chemical method provided important thermodynamics and structural information at variety of states, allowing understanding comprehensively the complex GP phenomena. Special emphasis in the paper content is dedicated to the phenomenology of the GP mass spectrometric ionization processes and thermodynamics of fragmentation molecular ions of CDs and their supramolecular self-assembly which, strongly depends on the experimental factors.