Aim of the study Egyptian medicinal plants are well known by their diverse uses in traditional folk medicine to cure various ailments including infectious diseases. Forty-two Egyptian medicinal plant species were selected from local market and were subjected to antiviral screening bioassay to investigate and to evaluate their biological activities. Materials and methods Hydro-alcoholic extracts of each species were separately prepared and tested against three viruses: herpes simplex-1 virus (HSV), poliomyelitis-1 virus (POLIO) and vesicular stomatitis virus (VSV). The antiviral activity were determined by means of the end point titration technique (EPTT) that depends on the ability of plant extract dilutions to inhibit the produced cytopathogenic effect (CPE) and expressed as reduction factor (Rf) of the viral titer. Results Achillea fragrantissima, Jasonia montana and Globularia arabica are found to have antiviral activity against POLIO in a concentration dependent manner at complete non-toxic concentration range 10–100μg/ml (Rf 106), 10–100μg/ml (Rf 105) and 50–100μg/ml (Rf 104), respectively while Tanacetum sinaicum are found to have moderate antiviral activity against POLIO at concentration of 50–100μg/ml (Rf 102). Ephedra alata and Moringa peregrina are found to have antiviral activity against HSV (Rf 104). Also, the results revealed that Capparis sinaica, Tamarix nilotica and Cyperus rotundus are found to have virucidal effect against HSV. All the forty-two plant species are found to have no reliable antiviral activity against VSV. Conclusion The specific indications claimed by the traditional healers are confirmed by antiviral test.