In the last two decades, global human health problems and economic disasters have been brought on by many viruses, such as severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and middle east respiratory syndrome coronavirus (MERS-CoV), belonging to coronaviruses, and influenza viruses mainly H1N1. The lack of specific therapies and few available treatments for these viruses have made them more difficult to overcome. A significant barrier to antiviral therapy is the emergence of drug-resistant respiratory viruses; as a result of naturally occurring mutations, in addition to the misuse of already approved antiviral drugs. Therefore, this study will be on Moringa oleifera leaf extract as one of the most common medicinal plants. The ethanolic extract of the plant leaf powder was prepared and fractionated, later the crude and the fractions were tested for antiviral activity against H1N1 and SARS-CoV-2 as the causative agent for pandemic 2009 and 2019, respectively, after safety confirmation on Madin-Darby canine kidney (MDCK) and African green monkey kidney derived cells (Vero-E6) cell lines. The plaque reduction assay was performed for the crude ethanolic extract to determine the action of the antiviral medication with a low IC₅₀. The results showed high safety on the two cell types and the activity against both viruses with high percentage of direct inhibition (virucidal), indicating that Moringa oleifera can represent a promising antiviral agent against them.