Background: Recurrent Herpes labialis (RHL), as a common herpes infection in healthy persons, is treated symptomatically. Melissa officinalis has antiviral effects may affect RHL. Objectives: The current double-blind randomized study aimed to compare the clinical effect of Melissa gel and 5% acyclovir cream to treat RHL. Materials and Methods:The current study was conducted on 60 healthy students of the faculty of dentistry and dormitory residents who had experienced RHL. Participants were randomly divided into group A (treated by Melissa gel) and group B (treated by 5% acyclovir cream). The subjects used the topical drugs for seven days; they were examined on the first, second, fourth and seventh days .Clinical parameters (size of lesion, pain severity, presence of erythema and healing time) were evaluated in each visit and their changes were recorded. Results: There were no significant differences between the two groups considering the changes in the size of lesions, healing time and erythema around the lesion (except on the fourth day). Pain severity alterations among the two groups showed significant differences on the second and forth days. Conclusions: Although Melissa gel effectively reduced pain severity on the second and forth days, it was not effective to treat RHL.