Dengue is a major mosquito-borne disease that currently has no effective antiviral or vaccine available. Recently, Indonesia is one of the largest countries in the dengue-endemic region, with a total population of more than 250 million. In the present study, the antiviral activity of P. merkusii stem bark and cone were evaluated against dengue virus type-2 (DENV-2; NCBI accession number: KT012509) isolated from Surabaya, Indonesia. We revealed that P. merkusii stem bark and cone inhibited DENV-2 in Vero cells (originally from African green monkey kidney) with IC50= 140.63 μg/mL and 73.78 μg/mL, CC50= 89.65 μg/mL and 249.5 μg/mL, SI= 0.64 and 3.38, respectively. The findings presented here suggest that P. merkusii stem bark and cone exerts potent antiviral activity against DENV-2. Hence, P. merkusii stem bark and cone are potent to inhibit DENV-2 and should be considered for in vivo evaluation in the development of an effective antiviral compound against DENV-2.