Nanomaterials have now found applications across all segments of society including but not limited to energy, environment, defense, agriculture, purification, food medicine, diagnostics, and others. The pandemic and the vulnerability of humankind to emerging viruses and other infectious diseases has renewed interest in nanoparticles as a potential new class of antivirals. In fact, a growing body of evidence in the literature suggests nanoparticles may have activity against multiple viruses including HIV, HNV, SARS-CoV-2, HBV, HCV, HSV, RSV, and others. The most described antiviral nanoparticles include copper, alloys, and oxides including zinc oxide (ZnO), titanium oxide, iron oxide, and their composites, nitrides, and other ceramic nanoparticles, as well as gold and silver nanoparticles, and sulfated and nonsulfated polysaccharides and other sulfated polymers including galactan, cellulose, polyethylenimine, chitosan/chitin, and others. Nanoparticles, synthesized via the biological or green method, also have great importance and are under major consideration these days, as their method of synthesis is easy, reliable, cost-effective, efficient, and eco-friendly, and is done using easily available sources such as bacteria, actinomycetes, yeast, fungi, algae, herbs, and plants, in comparison to chemically mediated synthesis. Chemical synthesis is highly expensive and involves toxic solvents, high pressure, energy, and high temperature conversion. Examples of biologically synthesized NPs include iron oxide, Cu and CuO NPs, and platinum and palladium NPs. In contrast to traditional medications, nanomedications have multiple advantages: their small size, increased surface to volume ratio, improved pharmacokinetics, improved biodistribution, and targeted delivery. In terms of antiviral activity, nanoscale interactions represent a unique mode of action. As reviewed here their biomedical application as an antiviral has shown four major mechanisms: (1) direct viral interaction prohibiting the virus from infecting the cell, (2) interaction to receptor or cell surface preventing the virus from entering the host cells, (3) preventing the replication of the virus, or (4) other processing mechanisms which inhibit the spread of virus. Here these pharmacologic mechanisms are reviewed and the challenges for technology translation are discussed in more detail.