A study is performed of the adsorption of water–methanol and water–acetonitrile mixtures on chiral stationary phases (CSPs) Chirobiotic R, Chirobiotic T, and Nautilus-E with grafted macrocyclic antibiotics ristocetin A, teicoplanin, and eremomycin, respectively. The patterns of adsorption on the indicated CSPs are qualitatively the same, and differ only by quantitative indicators. Adsorption isotherms of excess water from binary solvents have adsorption azeotrope points and show the preferred absorption of water in the range of pure organic component to an azeotrope point in the range of 60–75 mol % for H2О–МеОН and 80–90 mol % for H2O–MeCN systems. It is shown that the thickness of the adsorption phase in the first case is less than one nominal molecular layer (0.10–0.13 nm). For H2O–MeCN, it is 3–4 molecular layers (0.88–1.05 nm). Activity coefficients are calculated for the components of solutions in surface layers. The coefficients indicate the systems deviate considerably from the properties of an ideal adsorption solution. Reasons for this behavior are discussed.