Entropy generation during peristaltic flow of nanofluids in a non-uniform two dimensional channel with compliant walls has been studied. The mathematical modelling of the governing flow problem is obtained under the approximation of long wavelength and zero Reynolds number (creeping flow regime). The resulting non-linear partial differential equations are solved with the help of a perturbation method. The analytic and numerical results of different parameters are demonstrated mathematically and graphically. The present analysis provides a theoretical model to estimate the characteristics of several Newtonian and non-Newtonian fluid flows, such as peristaltic transport of blood.