Background <p>Denture stomatitis is a frequent inflammatory condition among denture wearers, commonly linked to <i>Candida albicans</i> colonization. Although sodium hypochlorite is an effective disinfectant, it may cause mucosal irritation and alter denture surface properties, prompting interest in natural alternatives. This study compared the antifungal efficacy of aqueous Miswak extracts (decoction and maceration) with 0.5% sodium hypochlorite against <i>C. albicans</i> biofilm on CAD-CAM processed polymethyl methacrylate (PMMA) denture base specimens.</p> Methods <p>An in vitro experimental design was conducted using 40 sterilized CAD-CAM PMMA specimens inoculated with a clinical isolate of <i>C. albicans</i>. Samples were randomly divided equally into four groups (<i>n</i> = 10): 0.5% sodium hypochlorite, Miswak decoction extract, Miswak maceration extract, and sterile distilled water (control). After 10&#xa0;min of immersion, colony-forming units (CFU/mL) were determined on Sabouraud Dextrose Agar. Data were analyzed using one-way ANOVA and Games-Howell post hoc tests (<i>p</i> &lt; 0.05).</p> Results <p>Results showed sodium hypochlorite eliminated <i>C. albicans</i> (5.85 log reduction; 99.999%). Miswak decoction and maceration achieved 1.43 log (≈ 96%) and 1.26 log (≈ 94.6%) reductions, respectively, both significantly higher than control (<i>p</i> &lt; 0.05), with no significant difference between them (<i>p</i> = 0.608).</p> Conclusions <p>Aqueous Miswak extracts demonstrated promising antifungal effects, suggesting potential as a natural, safe adjunct for denture disinfection.</p>