To investigate the effects of denture cleansers on the various properties of CAD/CAM and heat-polymerized polymethyl methacrylate (PMMA). Two different brands of heat-polymerized and two of milled PMMA were fabricated (n = 50), in total 200. Each group was randomly divided into five subgroups (n = 10): control groups (D1) kept in distilled water, cleaning tablets (D2, D3), neutral (D4) and acidic electrolyzed acid water (EAW) (D5). Surface roughness, hardness and flexural strength values were evaluated. Data were statistically analyzed with two-way ANOVA and Tukey post hoc test for comparison (p<0.05). The milled group showed significantly lower surface roughness, greater surface hardness, and higher flexural strength values than heat polymerized denture bases (p<0.05). The denture cleansers had no significant effect on the surface roughness values of the milled specimens (p>0.05), whereas the specimens in the heat-polymerized groups and treated with D5 showed greater surface roughness values compared with the other cleaning agents (p > 0.05). The denture cleansers had no significant effect on surface hardness and flexural strength of heat polymerize groups (p > 0.05). However, D2, D3 and D5 cleaning agent decreased the hardness values of the milled group (p<0.05) and D5 cleaning agent decreased the flexural strength of the milled group (p<0.05). It was observed that the applied denture cleansers affected the surface roughness, surface hardness, and flexural strength values of both denture bases but within a clinically acceptable value. CAD/CAM denture bases showed significantly higher physical and mechanical properties than to heat-polymerized base materials. Although the applied neutral EAW cleaners give desired results for denture bases, clinical studies are needed for biological compatibility.