Phytotherapeutics is widely used nowadays as an alternative to the current antifungal drugs to reduce their side effects. Curcumin, with its wide therapeutic array as antioxidant and anti-inflammatory agent, is one of the natural compounds that ha..s an antifungal effect, especially when being used at nanoscale to increase its bioavailability. Our research aimed to evaluate clinically and microbiologically the effect of using topical nanocurcumin suspension to treat oral candidiasis. After 4 days from induction of oral candidiasis (baseline), we randomly divided 39 female BALB/c mice into three groups of 13 animals; nanocurcumin, nystatin, and sham groups. All animals in nanocurcumin and nystatin groups received topical treatment twice daily for 10 days. Then, we performed clinical and microbiological evaluations at baseline, day 5, and day 10. By the end of treatment, our results revealed that nanocurcumin promoted a significant reduction in the number of candida colonies. There was no statistically significant difference neither clinically nor microbiologically between nanocurcumin and nystatin groups. In conclusion, nanocurcumin has a good antifungal effect as nystatin, however, its therapeutic efficacy takes a longer time to appear than nystatin. The enhanced bioavailability of curcumin at the nanoscale qualifies this nano-herb as a promising alternative therapy for oral candidiasis, evading nystatin-associated morbidity.