Introduction: Denture stomatitis is the most common type of chronic oral candidiasis. Ginger (Zingiber officinale) is an herbal plant with profound antioxidant, antibacterial, anti-inflammatory and antifungal effects with possible effects on Candida albicans. In this study, we aimed at comparing the efficacy of ginger and nystatin mouthwashes on denture stomatitis. Materials and Methods: In this randomized clinical trial, 30 patients with type II denture stomatitis were randomly assigned into two groups. Group 1 received ginger mouthwash (20 ml, 3 times a day for 20 days), while group 2 used nystatin mouthwash (500000 IU, 3 times a day for 20 days). The patients were visited on days 5, 10, 15, 20. In each follow-up visit, the length and width of erythema were measured using a digital caliper. Patients’ satisfaction with the treatment was evaluated at the end of the study. Results: During a 20-day treatment period, both treatments significantly reduced the width and length of the erythema (P<0.001); but the changes between groups were not significant (P=0.9 for both measurements). Patients receiving ginger mouthwash were significantly more satisfied with the outcome compared to those receiving nystatin mouthwash (86.7% vs. 13.3%, P<0.001). Conclusion: Although both mouthwashes have acceptable efficacy on denture stomatitis, patients were more satisfied with ginger use. Therefore, ginger mouthwash is recommended as an alternative to nystatin mouthwash in treatment of denture stomatitis.   Keywords: Denture stomatitis; Ginger; Nystatin; Mouthwash