Aim: To evaluate the efficacy of commercially available neem tablets and denture cleaners on the Candida albicans (C. albicans) biofilm present over the intaglio surface of complete dentures. Materials and methods: A total of 40 complete denture patients were selected, based on the cleansing criteria they were split into four groups (n = 10) for evaluation of efficacy of four denture cleansing methods. Group I (purified water) was taken as control group, group II had Clinsodent denture cleanser (8 hours/overnight), group III neem tablets (8 hours/overnight), and group IV Densive denture cleanser (15 minutes immersion time). Before and after the immersion procedure, samples were collected and cultured on Sabouraud dextrose agar media. The total candidal count [colony-forming unit (CFU)/4 cm²] was then determined. The data was analyzed using analysis of variance (ANOVA), Bonferroni test and paired t-tests. Results: The results showed significant decrease in colony count in group II, that is, the Clinsodent group followed by group III (neem tablets), group IV (Densive denture cleanser), respectively. Mean change of CFU was highest in group II, that is, 138000, whereas lowest in group IV, that is, 65000. The p-value < 0.05, for groups II, III, and IV shows significant decrease in candidal count. Whereas, group I, the control group, is showing nonsignificant results. Conclusion: In comparison to other denture-cleansing agents, Clinsodent was shown to have the highest anti-candidal efficacy. The results showed significant reduction in following order (Clinsodent>neem tablets>Densive>purified water) but none of them was able to completely eradicate the biofilm. Hence, for the total eradication of biofilm, a mix of chemical and mechanical cleaning should be employed. Clinical significance: Poor oral hygiene in edentulous mouth contributes to halitosis, increase denture plaque aggregation and denture stomatitis. Hence, effective method of denture cleansing should be known and employed for regression of plaque adhesion.