The global spread of viral diseases is a public health issue. Ribavirin (RBV) and mycophenolic acid (MPA) are well-known wide-spectrum antiviral agents. The present study evaluated the potential of bovine serum albumin (BSA) nanoparticles (NPs) as a vehicle to improve the efficacy of molecules with antiviral activity. The results demonstrated that NPs offer a promising strategy for the delivery of antiviral drugs, improving their stability and reducing toxicity compared to free agents. BSA-based NPs effectively encapsulated hydrophilic molecules such as MPA and water-soluble compounds such as RBV, achieving encapsulation efficiencies of 10% and 20%, respectively. The purified NPs exhibited a particle size between 60 and 100 nm and did not show toxicity at the evaluated concentrations. In cellular viral infection models against Zika virus (ZIKV), Junín virus (JUNV), vesicular stomatitis virus (VSV) and herpes simplex virus (HSV-1), the BSA-based NPs loaded with MPA or RBV demonstrated antiviral properties superior to those of non-encapsulated agents, as well as 100- and 200-fold effective dose reductions, respectively. These findings clearly indicate the potential of BSA NPs as a novel platform for the development of safer and more efficient antiviral therapies.