This paper reports the results of high-pressure experimental modeling of interaction between glaucophane schist and harzburgite or websterite for the evaluation of the influence of mantle material on the input–output of components and character of metasomatic transformations at the crust–mantle boundary in the subduction zone. In all experiments, glaucophane schist (proxy for oceanic crust) containing volatile components (H2O and CO2) incorporated in hydrous minerals (amphiboles, phengite, and epidote) and calcite was loaded into the bottom of each capsule and overlain by mantle material. During the experiments at a temperature of 800°C and a pressure of 2.9 GPa, which correspond to the conditions of a hot subduction zone, the schist underwent partial (up to 10%) eclogitization with the formation of the anhydrous assemblage omphacite + garnet + quartz ± magnesite ± potassic phase. Carbonate and a potassic phase were formed only in the experiments with websterite in the upper layer. A reaction zone was formed at the base of the websterite layer, where newly formed omphacite, quartz, and orthopyroxene replaced in part initial pyroxenes. Orthopyroxene and phlogopite (or an unidentified potassic phase) were formed in the reaction zone at the base of the harzburgite layer; among the initial minerals, only orthopyroxene relicts were preserved. Above the reaction zones produced by diffusion metasomatism, new phases developed locally, mainly at grain boundaries: newly formed orthopyroxene and magnesite were observed in harzburgite, and omphacite and quartz, in websterite. Alterations along grain boundaries extended much further than the reaction zones, which indicates that fluid infiltration dominated over diffusion in the experiments. The experiments demonstrated that the H2O–CO2 fluid with dissolved major components released from the glaucophane schist can produce mineral assemblages of different chemical compositions in mantle materials: Na-bearing in websterite and K-bearing in harzburgite. The complementary components, K2O and CO2 for the websterite layer and Na2O for the harzburgite layer, are fixed in the initial glaucophane schist layer. The distinguished separation of alkalis and CO2 at the crust–mantle boundary can affect the character of metasomatism in the mantle wedge, primary magma compositions, and the chemical evolution of the rocks of the subducting slab.