Despite the availability of an effective vaccine, hepatitis B virus (HBV) and herpesvirus (HSV) infections remain one of the foremost public health problems in the world. The antiviral activity of P. orbicularis, a Cuban endemic plant, has previously been reported but data on its phytochemical characterization and elucidation of antiviral metabolites are still lacking. In this work we identified the main phytochemical compounds responsible for the anti-HBV activity through a bioactivity-guided purification protocol. The aim of this work was to characterize the activity of Phyllanthus orbicularis Kunth against the HBV and HSV through the determination of the effect of different extracts and chemical fractions on the main viral markers in cell cultures. Total extract and fractions obtained by column chromatography were assayed for inhibition of HBV replication markers and HSV replication. The antiviral activity of active fractions was examined by detecting the effects on the levels of HBsAg and extracellular HBV DNA in stable HBV-producing human hepatoblastoma HepG2 2.2.15 cells, as well as on the level of HSV replication. P. orbicularis extract and active fractions contained mainly phenolic acids and flavonoids. The antiviral effects were attributed mainly to (-)-epicatechin-3-O-gallate, procyanidins and gallate derivatives. This research strength the potential of Phyllanthus orbicularis Kunth as source of antiviral compounds.