Background and aims: Herpes simplex type 1 (HSV-1) is one of the most common and contagious viruses in humans. Curcumin is a natural polyphenol that produces antiviral effects against various viruses, such as HSVs. Despite curcumin’s numerous effects and benefits, its insolubility has reduced its clinical effectiveness. During recent decades, significant progress has been made in nanodrugs, which has helped expand new delivery systems. This study investigated the in vitro antiviral activity of curcumin-loaded, folic acid-chitosan-coated selenium nanoparticles (SeNP) against HSV-1. Methods: Synthesized SeNPs loaded with curcumin and coated with folic acid-chitosan molecules were used in this experimental study. The studied groups comprised cells and the virus-containing curcumin, acyclovir, and NPs with or without curcumin. The cytotoxicity of the compounds was evaluated on Vero cells using the MTT assay. Antiviral activity was investigated using the MTT colorimetric assay, and the inhibitory effect on HSV-1 was studied using a 50% tissue culture infectious dose assay. Results: The results of this research demonstrated that curcumin (50% inhibitory concentration [IC50]=5.64 µg/mL) and curcumin-loaded SeNPs (IC50=1.15 µg/mL) exhibited satisfactory antiviral potential against HSV-1 in vitro, while curcumin-loaded, folic acid-chitosan-coated SeNPs produced no antiviral effect against HSV-1 due to increased cytotoxicity. Conclusion: Based on the findings, the curcumin and curcumin-loaded SeNPs had acceptable antiviral potential against HSV-1. Loading curcumin with SeNPs makes the compound more active at a lower concentration, and therefore, lower doses can be administered to treat HSV-1 infection.