Dengue is an arthropod-borne viral disease that has become endemic and a global threat in over 100 countries. To date, there is no universal vaccine nor an effective antiviral agent against this life-threatening disease. Bismuth derived chemical compounds have been showed to inhibit the helicase activity of SARS coronavirus in vitro. In this study, we have investigated the antiviral activity of bismuth compounds against dengue virus serotype 2. Evaluation of the antiviral activity was performed with three different assay conditions; attachment, post attachment and cidal assay that was determined through foci forming reduction assay and quantitative real time RT-PCR. The results have revealed that the bismuth compound has potential antiviral activity against DENV2 by inhibiting 89.7% of viral RNA copy number. The findings of the present study may exploit inherent towards the development of a future antiviral agent against dengue.