<p>Xerostomia is frequently associated with an increased risk of oral candidiasis caused by <i>Candida albicans</i>. Despite its high prevalence, current therapeutic options remain limited, with management largely dependent on saliva substitutes for symptomatic relief. </p><p><b>Objective</b></p><p> This in vitro study aimed to evaluate the effect of various saliva substitutes on <i>Candida albicans</i> biofilm growth. </p><p><b>Material and methods</b></p><p> Six commercially available saliva substitutes were evaluated using a standardized <i>Candida albicans</i> biofilm growth assay in a 96-well plate format. Experimental conditions were adapted to simulate the oral environment, including the formation of a salivary pellicle. Salivary pellicle formation was characterized by measuring mass deposition and viscoelastic properties, before and after rinsing with saliva substitutes, using Quartz Crystal Microbalance with Dissipation monitoring (QCM-D). Statistical analyses were performed using two-way ANOVA followed by Tukey’s post hoc test for biofilm data, and unpaired Student’s t-test for salivary protein content. </p><p><b>Results</b></p><p> Two oil-based substitutes (Aequasyal^® and Vea Oris^®) significantly enhanced Candida albicans biofilm formation compared to control (PBS) (<i>p</i> &lt; 0.05). QCM-D characterization of the salivary pellicle after rinsing revealed that this effect was associated with stable interactions between substitute components and the salivary pellicle, leading to structural modifications of the protein layer. </p><p><b>Conclusion</b></p><p>While oil-based saliva substitutes effectively alleviate xerostomia symptoms, they may unintentionally promote <i>Candida albicans</i> biofilm formation. Clinicians should exercise caution when recommending these products to patients with a history of oral candidiasis, favoring water-based alternatives especially in high-risk individuals.</p>