Medicinal herbs, Geum japonicum, Syzygium aromaticum, Terminalia chebula, and Rhus javanica, with anti-herpes simplex virus therapeutic activity, inhibited replication of human cytomegalovirus(CMV) and murine CMV(MCMV) in vitro. These anti-CMV activities were examined in an MCMV infection model using immunosuppressed mice. Geum japonicum, Syzygium aromaticum, and Terminalia chebula significantly suppressed MCMV yields in lungs of treated mice compared with water treatment. Efficacy of oral treatment with 750 mg/kg/day of Geum japonicum-extract was similar to that of the intraperitoneal administration with 2 mg/kg/day of ganciclovir in increasing the body weight of infected mice and reducing the virus yield in the lungs. These herbs may be beneficial for the prophylaxis of CMV diseases in immunocompromized patients.