The air humidification-dehumidification (HDH) technique for water desalination can be useful in many water production applications. Researchers from all around the world have examined various implementations of this technology to improve it. The present research investigates the effect of three dehumidifier coolants on the system. These coolants include water, helium, and hydrogen. The impact of these coolants on the parameters of the humidification-dehumidification desalination system will be discussed. The investigation’s parameters are tested at various mass ratios, air flow rates, and air outlet heaters. The results show that when hydrogen is employed as a dehumidifier coolant, the gained output ratio (GOR) achieves its peak of 6.37 in the considered mass ratio range of 2.1 to 3. On the other hand, when hydrogen is utilized as a dehumidifier coolant, the system produces the maximum entropy, with the dehumidifier contributing the most. When the mass ratio changes from 2 to 3, the average entropy generation for the system using hydrogen in the dehumidifier increases by 3.8 and 2.9 times, respectively, compared to the average entropy generation for the system using water and helium. However, when hydrogen is used as a dehumidifier coolant, safety concerns must be addressed, as well as the size and cost of heat exchangers in comparison to water.