AIM: The study aims to investigate the antiviral activity various extracts of six indigenous herbs used in Indian traditional medicine. METHODS: Crude extracts, methanolic, hydro-methanolic (1:1), aqueous-cold and aqueous-hot extracts of six indigenous herbs, were investigated for antiviral activity against H5N1 highly pathogenic avian influenza virus (HPAI) in an in vitro study. Each plant was tested at maximum non-cytotoxic concentrations (MNTC) in three different layouts to elucidate the virucidal, pre-exposure and post-exposure antiviral activity by their ability to reduce virus-induced cytopathic effect (CPE) in Madin Darby Canine kidney (MDCK) cells. Phytochemical analysis was carried out to identify the major compounds in the extracts. RESULTS: Out of 28 extracts tested, cold aqueous extract of bark of Acacia arabica var. indica revealed 100% virucidal activity at concentration 0.625 mg/ml and the hot aqueous extract of leaves of Ocimum tenuiflorum showed 58% inhibition at 2.5 mg/ml concentration and hot and cold aqueous extracts and hydro-methanolic extract of leaves of Azadirachta indica showed 42% (at 1.25 mg/ml), 58% (at 1.25 mg/ml), and 92% (0.325 mg/ml) inhibition, respectively. The phytochemical analysis of the extracts revealed presence of tannins and other phyto-ingredients which may be responsible for the antiviral activity. CONCLUSION: The present study is considered to be the first report for Indian traditional medicine plants screened as anti-influenza activity against HPAI virus. The phytochemical studies of the antiviral active ingredients in these medicinal plants will definitely facilitate in furthering the quest for identification of novel anti-viral formulations against HPAI.