In this work, we investigate the potential of highly sulfated synthetic glycomimetics to act as inhibitors of viral binding/infection. Our results indicate that both, long chain glycopolymers and short chain glycooligomers are capable of preventing viral infection. Notably, glycopolymers efficiently inhibit human papillomavirus (HPV16) infection in vitro and maintain their antiviral activity in vivo, while the glycooligomers exert their inhibitory function post attachment of viruses to cells. Moreover, when we tested the potential for broader activity against several other human pathogenic viruses, we observed broad-spectrum antiviral activity of these compounds beyond our initial assumptions. While the compounds tested displayed a range of antiviral efficacies, viruses with rather diverse glycan specificities such as Herpes Simplex Virus (HSV), Influenza A Virus (IAV) and Merkel Cell Polyomavirus (MCPyV) could be targeted. This opens up new opportunities to develop broadly active glycomimetic inhibitors of viral entry and infection.