In the present work, the formation of an interface region in the multilayer periodic Mo/Be mirrors was studied using X-ray photoelectron spectroscopy. The impact of a barrier B4C layer on the interdiffusion at both interfaces of the Mo/Be mirror (Mo-on-Be and Be-on-Mo) was analyzed in detail, paying particular attention to the interaction of the barrier B4C layer with the Mo and Be layers and accompanying oxidation processes. It was established that the barrier B4C layer (i) reduces the total amount of the beryllides at the interfaces, which is compensated by the appearance of MoB; (ii) limits the formation of the Be-rich MoBeα beryllide at the Be-on-Mo interface, making this interface more sharp; (iii) facilitates the formation of beryllium carbide Be2C at both interfaces; and (iv) partially protects the oxidation of the beryllium layer located under the Mo layer. Additionally, theoretical analysis of probable interface reactions and their products was performed. The results obtained within the framework of the proposed models correlate well with the experimental data. Despite the simplicity of the suggested approach, it exhibits satisfactory predictive power that can be exploited for material selection to improve the interface quality of multilayered structures.