In this study, the thermo-flow behaviours of the spiral tube were examined using water and some nanofluids such as TiO2, Al2O3, Fe2O3, CuO, ZnO, and CeO2. The computational flow dynamic modelling of the spiral coiled tube was performed with ANSYS 20 software program. The k–ε model with a standard wall function was used to simulate the thermo-flow characteristics. The solution of the governing equations was performed using the discretization method of finite volume. The study was carried out considering the case of fluid-to-fluid heat transfer in turbulent conditions. The influence of different key design parameters such as Reynolds number, different nanofluids, and flow arrangements was of main interest. The volume concentration of the nanofluids is 1%. The experiments were performed at different Reynolds ranges (9,000, 14,000, 20,000, and 25,000). The outlet temperature values, heat transfer coefficient, coefficient of friction, Nusselt number values of water, and nanofluids were found and compared. It was found that the outlet temperature, heat transfer coefficient, and Nusselt number values of water were the lowest, while the coefficient of friction value was the highest compared to the nanofluids. Among the nanofluids, CeO was found to have the highest outlet temperature, heat transfer coefficient, and Nusselt number value, as well as the lowest coefficient of friction value. TiO2 was found to have the lowest outlet temperature (T
out), the heat transfer coefficient value, and the highest coefficient of friction value. Al2O3 was found to have the lowest Nusselt number. In addition, Nusselt number values were obtained at different Dean numbers of water (2,200, 3,400, 4,900, 6,100, 7,350, and 8,600) and found to be compatible with previous studies. In addition, the coefficients of friction values of water at different velocities (0.18, 0.24, 0.41, 0.71, 0.95, 1.07, and 1.18) were obtained and found to be compatible with previous studies.