Superlattice interfaces can efficiently scatter phonons and filter low-energy electrons, thereby reducing the thermal conductivity to the “alloy limit” of crystalline solids and increasing the Seebeck coefficient substantially. In this paper, we report a two-fold reduction in the thermal conductivity and an improvement of about 170% in the Seebeck coefficient of an existing In₂O₃(ZnO)₉ superlattice by chemically modifying the interface with small additions of aluminum. Using a classical model for the interface transport, we attribute such significant changes to the increase in both the Kapitza (thermal) resistance and the electron potential barrier height of the InO₂⁻ superlattice interfaces that are modified by Al³⁺. The present work opens a new avenue of research showing that the superlattice interfaces can be chemically tuned for specific properties, which can be investigated in both experimental and computational ways, and also suggests a new route for material design for applications in areas like thermoelectrics.