The purpose of this study was to investigate the effect of different chemical intra-oral prosthesis cleansers on the surface properties of Parylene-C coated and non-coated polymethyl methacrylate (PMMA). A total of 120 PMMA samples were prepared. Half of the samples were coated with 10 µm of Parylene-C. Samples were exposed to either air (control) or one of two types of denture cleansers, an alkaline peroxide cleanser (Steradent) or a neutral peroxide cleanser with enzyme (Poligrip). Surface roughness (Ra) and surface free energy (SFE) values were measured and compared between groups. Scanning electron microscopy was used for visual analysis. The samples coated with Parylene exhibited significantly lower mean Ra values compared to the non-coated samples (p<0.001). Immersion in Steradent increased the roughness of non-coated PMMA, but its effect was minimized on the coated surfaces. SFE increased for the samples exposed to air and Poligrip, but decreased for the samples exposed to Steradent.