Medicinal plants extracts are interesting novel drugs for use as antimicrobial and antiviral agents. In this study we investigate the in vitro antiviral activity of eight ethanol medicinal plant extracts against Herpes simplex virus (HSV-1) infection on monkey kidney cells. Acyclovir, an antiviral agent currently applied for treatment of herpes virus type 1 infection, was used to compare the plant extracts therapeutic activity. The inhibitory concentrations (IC50) were determined for eight medicinal plants extracts obtained from the following plants: Calamintha origanifolia, Satureja thymbra, Prangos aspurela, Sidiritis Perfoliata, Aspurela glomerata, Erythreae Centaurium, Hyssopus officinalis and Salvia accetabulosa. Cytotoxicity was evaluated by MTT assay in Vero cells. The selective index (SI) of these medicinal plant extracts was used to prove the therapeutic activity. We found that C. origanifolia and S.thymbra extracts have the highest selective index (SI) in our data and are therefore potentially be used for treatment of HSV-1 disease