Dengue virus (DENV) belongs to the genus Flavivirus (family of Flaviviridae). DENV causes dengue fever, which may lead to a severe dengue hemorrhagic fever. Recently, there has been any discovery on effective antiviral drugs to treat dengue fever and therapy used to treat it only limited to replacement of body fluids. This research is looking for NS5 RdRp protein inhibitors responsible for the synthesis of intermediate RNA for subsequent replication of the positive-strand RNA genome through a virtual screening approach. In this study, four NS5 RdRp proteins from each DENV serotypes were collected. DENV serotype 2 NS5 RdRp was collected from the RCSB PDB database with PDB ID:5K5M, while the others were modeled based on protein sequence collected from NCBI database. About 343,798 natural product compounds from ZINC15 database were screened through computational study according to the Lipinski's Rule of Five, drug likeness, and toxicity properties, followed by molecular docking simulation to determine the potential natural product compounds as a lead compound. This study obtained three compounds, namely Compound 3556, Compound 9487, and Compound 106665, which had good inhibitory activity on NS5 RdRp protein compared to SAM and SAH. Furthermore, the docking simulation also revealed that Compound 3556 gave the best ligand interaction and had the lowest Gibbs free binding energy (ΔG binding) at -11.1618 kcal/mol. Thus, Compound 3556 can be proposed as novel drug candidates for inhibiting NS5 RdRp.