Skin dendritic cells (DCs) are primary target cells of dengue virus (DENV) infection and they play an important role in its immunopathogenesis. Monocyte-derived dendritic cells (MDDCs) represent dermal and bloodstream DCs that serve as human primary cells for ex vivo studies of DENV infection. Improved understanding of the mechanisms that effectuate the inhibition of DENV replication in MDDCs will accelerate the development of antiviral drugs to treat DENV infection. In this study, we investigated whether or not vivo-morpholino oligomer (vivo-MO), which was designed to target the top of the 3' stem-loop (3' SL) at the 3' UTR of the DENV genome, could inhibit DENV infection and replication in MDDCs. The findings of this study revealed that vivo-MO-1 could inhibit DENV-2 infection in MDDCs, and that it could significantly reduce DENV RNA, protein, and viral production in a dose-dependent manner. Treatment of MDDCs with 4 μM of vivo-MO-1 decreased DENV production by more than 1,000-fold, when compared to that of the vivo-MO-NC control. Thus, vivo-MO-1 targeting of DENV RNA demonstrates potential for further development into an anti-DENV agent.