Objectives: This study aimed to evaluate the changes of surface roughness and hardness of conventional heat-cured (CHC) and CAD/CAM PMMA after immersion in alkaline peroxide chemical denture cleansers (DC), simulating one -year of use. Materials and Methods: 30 specimens of CHC, and another 30 specimens of CAD/CAM PMMA were divided into three groups (n= 10), each were immersed in two commercially available alkaline peroxide DC (Corega tablets and Polident tablets) as well as distilled water (control group). The mean surface roughness (Ra) of the specimens was recorded using contact stylus surface analyzer device. The surface hardness (VHN) was recorded using Vickers micro-hardness tester. T‑test for paired observation and independent samples T-test were used to indicate and compare any changes in Ra and hardness between the baseline and after simulated daily immersion in DC for one-year. Results: The tested DC had no significant effect on the Ra and hardness of CAD/CAM PMMA specimens. But both types of DC produced significant increase in Ra and significant decrease in VHN of the CHC PMMA specimens (P < 0.05). The Ra of the CAD/CAM PMMA specimens was significantly lower and the VHN was significantly higher than that of the CHC PMMA after treatment with DC. Conclusions: Alkaline peroxide DC appears not to affect the Ra and hardness of CAD/CAM PMMA. Alkaline peroxide DC produced negative effect on the Ra and hardness of CHC PMMA. CAD/CAM denture base resins might be considered the material of choice to produce more durable dentures.