Introduction: In children, polymethylmethacrylate (PMMA) is a commonly used material for fabrication of dental prostheses, such as obturators, removable space maintainers, habit-breaking appliances, removable orthodontic appliances, and removable partial and complete dentures. Regular cleaning of such prostheses is vital for maintaining the health of the oral tissues as well as the longevity of the prosthesis. The chemical method of disinfection, using different chemical cleansers, is commonly used for cleaning a dental prosthesis. Some of these disinfecting agents have been reported to alter the physical and mechanical properties of PMMA. Aim: The aim of the study was to analyze the effect of two commonly used disinfecting agents on the surface roughness and surface hardness of two PMMA-based materials processed using different curing cycles. Materials and methods: PMMA samples were made using short and long curing cycles. The surface roughness and hardness of the samples before and after immersion in the two disinfecting agents were recorded. A profilometer was used to measure surface roughness, whereas hardness was measured using the Vickers hardness tester. Results: Both disinfecting agents increased the surface roughness and decreased the hardness of the PMMA samples. The effect was more profound in samples made using the short curing cycle. Conclusion: It is important to select the appropriate disinfecting agents and follow the manufacturers’ instructions to ensure that the other properties of the prosthesis are not affected.