Objective <p>This study aimed to assess the effects of various denture cleansers on the color stability, surface roughness, microhardness, and antibacterial activity of polymethyl methacrylate (PMMA) denture base materials modified with titanium dioxide TiO₂ nanoparticles.</p> Materials and methods <p>Ninety disc-shaped PMMA specimens (10 × 10 × 2&#xa0;mm) were fabricated and divided into three groups based on TiO₂ concentration: 0% (control), 3%, and 5%. Each group was further subdivided based on the cleanser used: distilled water, Corega oxygenating tablets, or 0.5% sodium hypochlorite (n = 10). Measurements of color change (ΔE, using the CIE L<i>a</i>b* system), surface roughness (Ra), microhardness (Vickers hardness test), and antibacterial activity (zone of inhibition against <i>Streptococcus mutans</i> and <i>Candida albicans</i>) were conducted at 90 and 180&#xa0;days. Statistical analysis included one-way ANOVA and Tukey’s post hoc test (α = 0.05).</p> Results <p>Sodium hypochlorite induced the most significant color changes and surface roughness, particularly in the unreinforced group. TiO₂-reinforced samples demonstrated improved resistance to surface degradation and maintained higher microhardness values, especially with 5% nanoparticle concentration. Chemical cleansers reduced antibacterial activity slightly, but TiO₂-containing samples still exhibited superior efficacy compared to controls.</p> Conclusion <p>The incorporation of TiO₂ nanoparticles enhances the durability, aesthetic stability, and antimicrobial properties of PMMA denture base materials. However, cleanser selection plays a critical role in preserving these properties. Sodium hypochlorite, while effective, may compromise surface integrity. Enzymatic and non-abrasive cleansers are more suitable for long-term use with nanoparticle-reinforced denture bases.</p>