AbstractSurface roughness has a great impact on the peristaltic motion of nanofluid flow and plays an important role in engineering, manufacturing, and material sciences. During tissue engineering, imaging techniques, implant surface finish, surgical instrument texture, and tissue engineering, and so forth. This study explores the effects of electrical double layers, surface roughness, velocity slip, and thermal slip to investigate the heat transfer rate of cobalt and alumina nanoparticles with water through uniform and nonuniform horizontal tubes. In the present study, the Jeffrey nanofluid flow model is chosen to investigate the heat transfer phenomenon of hybrid nanofluids based on alumina and cobalt nanoparticles suspension in water. The effects of electroosmosis, surface roughness, viscous dissipation, heat source/sink parameter, velocity, and thermal slips are also under consideration during the peristaltic motion of hybrid nanofluid in uniform and nonuniform tubes. The mathematical software MATHEMATICA 13.3 is utilized to find the exact solution and graphical results to investigate the complicated flow behavior. It is noticed that the velocity near the walls of the tube is lower for the surface roughness parameter and higher in the core part. The behavior of velocity for the remaining parameter is the opposite. The temperature of the current fluid flow increases for all parameters except the surface roughness parameter. The effects of velocity for hybrid nanofluid are prominent as compared with nanofluid in the core part. The temperature profile and heat transfer rate for hybrid nanofluids are lower as compared with nanofluids, which shows the cooling effects. This study is beneficial for hyperthermia, gene therapy, drug delivery, and tissue engineering.