The antiviral potential of pomegranate ethanolic extracts was monitored against herpes simplex virus type 1 (HSV-1) and hepatitis A virus (HAV). GCMS was performed to monitor the bioactive containment. Cell viability and antiviral activity of these extracts were assessed using endpoint assay, plaque reduction, and virucidal approaches against the target viruses. The IC50 of seed extract was about 31.216 mg/ml. HAV and HSV-1 infectivity titers were reduced by 23.50% and 25.%, respectively. While PSE reduced HAV and HSV-1 by 11.66% and 5.55%, respectively, using the direct method and 41.17% and 25% using the indirect method, PSE reduced HAV and HSV-1 titers by 29.33% and 11.17%, respectively. Upon inspection, it was noted that the myxovirus resistance protein (MX-A gene) expression levels were significantly elevated in PPE/PSE treated cells compared with negative control. Moreover, the concentration of oxidative stress biomarkers, including Glutathione Reductase (GSH), Reactive Oxygen Species (ROS), Malondialdehyde (MDA), and Nitric Oxide (NO), were assessed in PPE and PSE-treated Vero cells compared to negative control cells. The results indicated that pomegranate peel could be a promising herbal medicine ingredient targeting HAV and HSV-1, showing greater efficacy than pomegranate seeds. The integration of bioactive products was considered using molecular docking analyses.