Herpes simplex virus -2 (HSV-II) increases the prevalence of life-threatening viral infections so; there is a great need to find and develop new compounds to combat them. This study aims to compare the chemical composition, antioxidant potential and cell-mediated blocking of HSV-II activities of Alpinia officinarum (AO) and Zingiber officinale (ZO) root extracts. Phenolic and flavonoid contents were determined; antioxidant was evaluated by DPPH• (2,2-diphenyl-1-picryl-hydrazyl-hydrate) as well as investigation of HSV-II antiviral activity. The phenolic content in ethyl acetate extract for AO and ZO (114.40 ± 8.11 and 90.42 ± 9.67 mg GAE/g dry extract, respectively) was higher than in methanol (MeOH). Total flavonoid was promising in both plants; ethyl acetate extract (EtOAc) showed high flavonoid content (299.11 ± 33.85 and 147.92 ± 24.50 mg RE/g dry extract, respectively). IC50 of DPPH• scavenging activity was promising for AO and ZO EtOAc (23.78 and 30.03 µg/ml, respectively). The highest anti-HSV-II activity was AO EtOAc (91.9 %), followed by ZO EtOAc (50.3 %). Quantification of phenolic acid in ethyl acetate extract for plants by HPLC shows that the most prevalent phenolic compounds in ZO were Ellagic acid, Hesperetin, Querectin, Daidzein and Syringic acid (31.89, 22.91, 19.56, 18.49 and 11.33 µg/ml, respectively). While, the high content of phenolic acids in AO were Chlorogenic acid, Ellagic acid, Hesperetin, Apigenin, Syringic acid and Kaempferol (44.57, 42.05, 38.50, 29.91, 28.25 and 23.33 µg/ml, respectively). Both plants especially AO EtOAc extract were promised against HSV-II that may be returned to the presence of phenolic and flavonoid compounds.