The objective of the present numerical study is to investigate the heat transfer enhancement, entropy generation, and thermal performance of turbulent nanofluids inside double-pipe heat exchangers equipped with novel perforated cylindrical turbulators. Effects of inflow velocity, CuO nanoparticles volume fraction and perforated index are evaluated on the Nusselt number, friction loss, thermal performance factor (η), and viscous irreversibilities of the double-pipe heat exchangers. The newly proposed perforated turbulators with CuO nanopowder with ϕ = 1.5% provide the thermal performance of η = 1.931, which is considerably higher than the other previous studies. The results show that raising PI reduces the turbulent kinetic energy, especially in outer regions of the cylindrical turbulator. The jet formation near the walls and the perforations is the primary physical reason for this. The viscous entropy generation is increased up to 153.0% by increasing the Re number from 6,000 to 17,000 for PI = 8% and DR = 0.7. Thermal boundary layer disruption is the primary physical reason for heat transfer enhancement.