Recurrent herpes labialis (RHL) is a lifelong oral health issue that affects about one-third of the world’s population, causing frequent, painful, and discomfort lesions. This randomized, triple-blinded study aimed to evaluate the effectiveness of olive leaf extract (OLE) compared to acyclovir cream (Veramid 5%) in managing vesicular stage of RHL lesions. Forty patients were randomly divided into two equal groups and were instructed to apply the prescribed medication five times a day for five consecutive days. The evaluation was carried out by measuring the pain intensity on the first day before the treatment was applied (T0), 48 h (T1), and 7 days later (T2). Additionally, the day when the pain completely healed and the day when the lesion’s crust fell off spontaneously were recorded. Statistical analysis was conducted using the Mann-Whitney test at a significance level of α = 0.05. The study results indicated that there were no significant differences in pain intensity between the two groups during the three evaluation times: T0 (P = 920), T1 (P = 0.596), and T2 (P = 1.00). Furthermore, there was no significant difference in the day when the pain was completely healed (P = 0.697). However, the OLE showed a statistically significant advantage regarding the day the lesions’ crust fell off (P = 0.040). In conclusion, OLE may be a potential alternative treatment for RHL.Trial registration: isrctn.com ID: ISRCTN87606522, 04/09/2023.
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