This article studied a numerical estimation of the double-diffusive peristaltic flow of a non-Newtonian Sisko nanofluid through a porous medium inside a horizontal symmetric flexible channel under the impact of Joule heating, nonlinear thermal radiation, viscous dissipation, and heat generation/absorption in presence of heat and mass convection, considering effects of the Brownian motion and the thermophoresis coefficients. On the other hand, the long wave approximation was used to transform the nonlinear system of partial differential equations into a nonlinear system of ordinary differential equations which were later solved numerically using the fourth-order Runge–Kutta method with shooting technique using MATLAB package program code. The effects of all physical parameters resulting from this study on the distributions of velocity, temperature, solutal concentration, and nanoparticles volume fraction inside the fluid were studied in addition to a study of the pressure gradients using the 2D and 3D graphs that were made for studying the impact of some parameters on the behavior of the streamlines graphically within the channel with a mention of their physical meaning. Finally, some of the results of this study showed that the effect of Darcy number $$Da$$
Da
and the magnetic field parameter $$M$$
M
is opposite to the effect of the rotation parameter $$\Omega$$
Ω
on the velocity distribution whereas, the two parameters nonlinear thermal radiation $$R$$
R
and the ratio temperature $${\theta }_{w}$$
θ
w
works on a decrease in the temperature distribution and an increase in both the solutal concentration distribution, and the nanoparticle's volume fraction. Finally, the impact of the rotation parameter $$\Omega$$
Ω
on the distribution of pressure gradients was positive, but the effect of both Darcy number $$Da$$
Da
and the magnetic field parameter $$M$$
M
on the same distribution was negative. The results obtained have been compared with the previous results obtained that agreement if the new parameters were neglected and indicate the phenomenon's importance in diverse fields.