Developing flexible electromagnetic interference shielding (EMI SE) materials is an effective strategy to protect humans from being harmed by electromagnetic radiation from electronic devices. Though the EMI SE property of such materials as graphene can exceed 100 dB, it remains a challenge to achieve high-efficiency EMI SE performance while having excellent flexibility to allow them to be wearable. Herein, we designed theoretically and fabricated experimentally the flexible multilayer structure of the poly(vinylidene fluoride)/graphene-poly(vinylidene fluoride) (PVDF/GNP-PVDF) composite films. The experimental results show that the film thickness and layer number play an important role in determining the EMI SE performance, and the multilayer film with a thickness of 0.3 mm and a layer number of 6 exhibits not only high EMI SE performance (69.7 dB on average in X-band) but also excellent flexibility and stability (98.85% EMI SE retention after bending of 60° for 1000 cycles). The theoretical study via COMSOL software matching well with the experimental data reveals that multiple reflection and absorption of electromagnetic waves between layers is responsible for the high EMI SE performance of the PVDF/GNP-PVDF multilayer film at a relatively low thickness that ensures flexibility. This work highlights the significance of designing the multilayer architecture via theoretical simulation for improving the EMI SE performance and also demonstrates the high EMI SE application prospect of PVDF/GNP-PVDF films in wearable electronic devices.