In recent years, researchers have been seeking new sources for the treatment of viral infections, such as compounds obtained from plant extracts, fungi and algae and their chemically modified derivatives. Many of these compounds have already been studied in vitro exhibiting low toxicity and high inhibitory effect, including resistant viral strains. In the present study, the cytotoxicity, and antiherpetic activity of the natural polysaccharide (PN) obtained from Morinda citrifolia and its chemically sulfated derivative (PNCS) in Vero cells were evaluated. Cell viability and percentage of viral inhibition (% IV) were determined by MTT assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]. For cytotoxicity, represented by 50% cytotoxic concentration (CC50), cells were treated with varying concentrations of the test compounds. The antiviral activity, represented by 50% inhibitory concentration (IC50), cells were infected and simultaneously treated with test compounds at 1000 µg/mL to 250 µg/mL. For both experiments, Vero cells cultivated in 96 well microplates were incubated at 37°C with 5% CO2 for 72 h, followed by MTT assay and absorbance read at 570nm and 690nm. Cell viability was determined by the absorbance of compound-treated cells compared to control cells (untreated cells) and the %VI by the absorbance of the cells infected and treated in comparison to the absorbance of infected and untreated cells. The CC50 and the IC50 were determined by linear regression of the generated curves and the selectivity index (SI) by the ratio between CC50/IC50. Both compounds tested did not show cytotoxicity up to the maximum concentration tested, presenting CC50> 1000 μg/mL. When the compounds were evaluated for anti-herpetic activity, only PNCS showed significant % IV of 73.3% and 43.7%, at concentrations of 1000 μg/mL and 500 μg/mL, respectively, with IC50 of 505 μg/mL and SI> 2. The PN showed low % IV (20%), in the same concentrations analyzed. The antiviral activity of extracts of M. citrifolia has already been demonstrated against dengue and hepatitis C. However, anti-herpetic activity had never been evaluated before. New anti-herpetic studies should be performed with other chemical modifications, including changes in the degree of sulfation of PNCS to improve IS and suggest a possible mechanism of action of M. citrifolia.