This work analyzes the non-isothermal electro-osmotic fluid flow in a microchannel considering the Soret effect and temperature-dependent properties. The constitutive equation that models the fluid rheology corresponds to the generalized Phan-Thien–Tanner (gPTT) model. Temperature and pressure gradients are induced due to the interaction between an ionized fluid and the electrical field imposed at the microchannel's ends, resulting in Joule heating. The temperature-dependent physical properties of the fluid modify the ionic distribution in the electric double layer and its thickness change along the microchannel walls. The generalized Phan-Thien–Tanner (gPTT) model is used as a constitutive equation that describes the fluid rheology, where the trace-stress tensor is based on the Mittag–Leffler function, which represents the destruction of physical junctions and entanglements in the Lodge–Yamamoto network of viscoelastic fluids, through the inclusion of two fitting parameters: α and β. The gPTT model allows better fitting and flexibility to experimental data and a wider range of variation in the description of rheological responses of complex fluids. The hydrodynamics and thermodiffusion obtained through the gPTT model are compared against that using the linear form of the Phan-Thien–Tanner model (lPTT).