Herpes simplex virus type 1 (HSV-1) causes serious infections particularly in immunocompromised patients. Methanolic extract of four plants were evaluated for their anti-viral effects against acyclovir resistant HSV-1 in HeLa cell line. The 50% cytotoxic concentration (CC50) as well as the effective minimal cytotoxic concentration of each plant extract were evaluated by MTT assay. Antiviral effects of the plant extracts on HSV-1 were examined at different concentrations of the extract. The effective minimal cytotoxic concentration was evaluated at different times of virus replication after infection. Virus titration was assessed by tissue culture infectious dose 50 (TCID50) method. Among the 4 plant extracts evaluated only Mentha pulegium L. extract was shown to exert the highest antiviral activity, with selectivity index (SI) 10.25. Direct treatment of HSV-1 with Mentha pulegium L. extract resulted in 1.7 log10 TCID50 reduction in virus titers after one hour. The highest reduction in HSV-1 infectivity was obtained 1 hour after the infection of the cells with virus resulting in 2.1 log10 TCID50 reduction as compared to the control. The antiviral effects of Mentha pulegium L. extract on HSV-1 after virus infection was more remarkable than the virucidal activity.