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A theoretical and a mathematical model is presented to determine the entropy generation on electro-kinetically modulated peristaltic propulsion on the magnetized nanofluid flow through a microchannel with joule heating. The mathematical modeling is based on the energy, momentum, continuity, and entropy equation in the Cartesian coordinate system. The effects of viscous dissipation, heat absorption, magnetic field, and electrokinetic body force are also taken into account. The electric field terms are helpful to model the electrical potential terms by means of Poisson–Boltzmann equations, ionic Nernst–Planck equation, and Debye length approximation. A perturbation method has been applied to solve the coupled nonlinear partial differential equations and a series solution is obtained up to second order. The physical behavior of all the governing parameters is discussed for pressure rise, velocity profile, entropy profile, and temperature profile.