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Wild Piper nigrum belongs to the family Piperaceae and is naturally distributed in India in the Western Ghats. The Phytochemical study has shown that the extracts of Piper species enhance the bioavailability of certain drugs. Work has not been carried out on antimicrobial and antiviral activity of Oleoresin extracted from root and stem of wild Piper nigrum. Therefore in the present study Oleoresin was extracted from the roots and stem of wild Piper nigrum collected from Agumbe forest of Karnataka. The extracted Oleoresin has been evaluated for its in vitro antimicrobial activity using the Filter paper disc method and Cut well method. Five bacteria (Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Salmonella typhi and Staphylococcus aureus ) and five fungi (Aspergillus niger, Aspergillus flavus, Penicillium spp, Drechslera spp and Fusarium spp) were used as test organisms in the assay. The results revealed good antibacterial activity compared to its antifungal activity. Oleoresin showed maximum activity against B. subtilis and Penicillium spp. Dengue is caused by an RNA virus named Flavivirus from Flaviviridae. Currently, there is no licensed drug available and to date, several vaccine candidates are still under development against the Dengue virus (DENV). So an attempt was done to test the inhibitory activity of Oleoresin against DENV protease 2VBC by In silico docking. This revealed potent inhibitory activity of Oleoresin against DENV protease 2VBC with the binding energy of -7.2kcal/mol. Furthermore, the study indicated that the potent inhibitor can be subjected to chemical modifications and tested for its cytotoxicity assay by in vitro studies. It is worth attempting to study the effects of this bioactive compound on as many bacteria and fungi as possible so that the potency of the compound could be fully understood and applied in drug development.