A theoretical study is presented to examine entropy generation in double-diffusive convection in an Electro-osmotic flow (EOF) of nanofluids via a peristaltic microchannel. Buoyancy effects due to change in temperature, solute concentration and nanoparticle volume fraction are also considered. This study was performed under lubrication and Debye-Hückel linearization approximation. The governing equations are solved exactly. The effect of dominant hydrodynamic parameters (thermophoresis, Brownian motion, Soret and Dufour), Grashof numbers (thermal, concentration and nanoparticle) and electro-osmotic parameters on double-diffusive convective flow are discussed. Moreover, trapping, pumping, entropy generation number, Bejan number and heat transfer rate were also examined under the influence of pertinent parameters such as the thermophoresis parameter, the Brownian motion parameter, the Soret parameter, the Dufour parameter, the thermal Grashof number, the solutal Grashof number, the nanoparticle Grashof number, the electro-osmotic parameter and Helmholtz–Smoluchowski velocity. The electro-osmotic parameter powerfully affected the velocity profile. The magnitude of total entropy generation increased as the thermophoresis parameter and Brownian motion parameter increased. Soret and the Dufour parameter had a strong tendency to control the temperature profile and Bejan number. The findings of the present analysis can be used in clinical purposes such as cell therapy, drug delivery systems, pharmaco-dynamic pumps and particles filtration.