This study evaluated the antiherpetic activity and genotoxicity of catechin and some of its derivatives using the MTT colorimetric and comet assays, respectively. The results showed that all compounds have antiviral activity with selective indices varying from 1.3 to 13, depending on the tested HSV-1 strain. It was observed that the same concentration of the compounds that protects the Vero cells against the viral infection induces genotoxicity. It was also observed that the molecules containing three hydroxyl groups on the B ring caused less DNA damage and showed better antiviral effect than those with two hydroxyls on the same ring, but if there is an additional galloyl group, these results can be altered. The bioavailability and stereochemistry could be related to the antiviral and genotoxic effects detected.