The aim of this study was to determine the possibilities of using cold-plasma technology in counteracting the development of denture stomatitis (DS) in patients using different kinds of prosthetic restorations. The study focused mainly on the effect of cold atmospheric plasma on prosthetic materials, such as acryl (AR), acetal (AT), and a prosthetic metal alloy (MA). The materials were tested in terms of the effect of the plasma exposure time (5, 10, and 20 min) on changes in the chemical composition, morphology, and surface topography (FT-IR, SEM-EDS, optical profilometer) as well as changes in the color and contact angle (spectrophotometer, goniometer) after the plasma process. Furthermore, the ability of reference fungi (C. albicans and C. glabrata) to adhere to non-modified and cold atmospheric plasma (CAP)-modified dental materials was examined to evaluate the susceptibility of dental material surfaces to 12 h fungal contamination. The obtained results demonstrate that CAP appears viable for the surface modification of the acetal resin and the metal alloy, not compromising their structural integrity while variably limiting fungal overgrowth involved in the development of DS, whereas its application to the acrylic resin may be inadvisable due to morphological and optical alterations.