In this study, nanofluids formed by using ethylene glycol and three kinds of nanoparticles such as Al2O3, SiO2, and TiO2 were added to the four-stroke internal combustion engine radiator and compared with the conventional coolant (pure water). This comparison is based on the exergy performances which are the main theme of the second law of thermodynamics. The tests were carried out at a fixed engine speed of 1800 rpm using diesel fuel, and the outputs were obtained from the test setup experimentally. A total of six nanofluid tests were performed on two different dispersions (0.2% and 0.4%). As a result of this study, the best exergy efficiency was obtained by using TiO2 particles with a 35.67% value. Increasing the percentage of nanoparticles in the fluid from 0.2 to 0.4 positively affected efficiency. Pure water generally lagged behind nanofluid performance in experimental parameters. Compared to conventional coolant (pure water), the lowest exhaust temperature value was measured by using an Al2O3/Ethylene Glycol mixture with a difference of 59 K. Also, by using Al2O3 nanoparticles as a coolant, 8.858 kW of exergy exhaust value was obtained. This is the best emission value measured in the experimental study. While calculating values close to each other in the use of other nanoparticles, the worst exergy exhaust results were obtained by using the conventional refrigerant. Consequently, in this paper, exergetic outputs such as exergetic efficiency, exergy destruction, exergy heat, exergy work, exergy total exhaust, and entropy production rate were calculated for pure water and each nanofluid.