The friction factor, thermal performance, and heat transfer are experimentally analyzed for reduced-graphene oxide/cobalt oxide (rGO/CO3O4) hybrid nanomaterial-based nanofluid circulating in a plain tube with and without twisted tape inserts having different pitches. The reduced-graphene oxide/cobalt oxide (rGO/CO3O4) hybrid nanomaterial is prepared using in situ/chemical reduction technique and then characterized with transmission electron microscope, X-ray diffraction, and magnetometry. The experiments were conducted with different values of particle loading (0.05%, 0.1%, and 0.2%) and Reynolds number (2000–2,020,000). Three twisted tape inserts of helixes 285 mm, 190 mm, and 95 mm were used. The nanofluids was produced from the addition of the hybrid nanomaterial to water yield an increase, as compared to the basefluid (water), of the Nusselt number, which is further enhanced by increasing the nanoparticle loading. Therefore, when compared to water, the Nusselt number is enhanced by 25.65%, with no twisted tape and by 79.16% with twisted tape with helix of 95 mm for the nanofluid of 0.2% volume concentration. However, when compared to water, there is a slight friction factor penalty with the 0.2% particle loading of 1.11-times and 1.49-times for the plain tube and for the 95-mm twisted tape helix, respectively. The thermal performance factor gets enhanced by increasing the nanoparticles concentration of the hybrid nanofluids with or without twisted tape inserts, and it is always higher than one. Based on the experimental data, regression equations were developed for the Nusselt number and friction factor.