Denture hygiene is crucial for preventing oral infections, with Candida albicans being a common fungal pathogen that can colonize denture surfaces. This in vitro study evaluated the adherence of C. albicans on two denture base materials—polyamide and polymethyl methacrylate (PMMA)—and assessed the antifungal efficacy of various chemical and natural cleansers. A total of 100 polished specimens were inoculated with C. albicans and treated with chemical agents (Listerine at 2%, 20%, 50%; Corega^®, Block Drug Company, Jersey City, NJ, USA); Protefix^®, Queisser Pharma, Flensburg, Germany and natural products (15% apple vinegar, 2% tea tree oil, 2% peppermint oil) for different durations (5, 15, 30, 480 min). Chlorhexidine (2%) and untreated samples served as positive and negative controls, respectively. Corega^® and 15% vinegar eliminated C. albicans within 5 min on both materials. 50% Listerine was effective after 5 min on PMMA but required 480 min on polyamide. Protefix^® showed full efficacy in 5 min on PMMA and 30 min on polyamide. Tea tree oil required 30–480 min for activity, while peppermint oil showed minimal effect throughout. Under the tested conditions, Corega^® appeared most effective. Natural cleansers, particularly vinegar and tea tree oil, also showed considerable anticandidal potential, suggesting they may serve as alternative agents for denture hygiene applications.