This article presents the theoretical analysis of two-dimensional peristaltic transport of two-fluids in a flexible tube under the influence of electro-osmotic force. The flow domain is composed of two regions, namely, the core region and the peripheral region. The Newtonian and the FENE-P models are used to describe the rheology of fluids in the peripheral and the core regions, respectively. Governing flow equations corresponding to each region are developed under the assumption of long wavelength and low-Reynolds number. The interface between the two regions is computed numerically by employing a system of non-linear algebraic equations. The influence of relevant controlling parameters on pressure gradient, interface, trapping, and reflux is highlighted graphically and explained in detail. Special attention is given to estimate the effects of viscoelastic parameter of the core region fluid in the presence of electro-osmotic environment. Our investigation indicates an augmentation in the pressure loss at a zero volumetric flow rate with growing the viscoelastic and occlusion parameters. Moreover, trapping, reflux, and pumping efficiency are found to increase by increasing the electro-osmotic and viscoelastic parameters. The analysis presented here may be helpful in controlling the micro-vascular flow during the fractionation of blood into plasma (in the peripheral layer) and erythrocytes (core layer). This study may also have potential applications in areas such as electrophoresis, hematology, design, and improvement of bio-mimetic electro-osmotic pumps.