Indonesia is one of many tropical countries that have a high prevalence of four different serotypes of dengue virus (DENV). DENV infection may cause dengue hemorrhagic fever (DHF) and eventually lead to the death. The latest report shows that the number of DHF incidences in Indonesia was increased rapidly from 1968 to 2013. Therefore, an effective treatment is needed to medicate and repress the mortality rate from infection. The inhibition of host endoplasmic reticulum α-glucosidase II (α-Glu II) could be a potential approach for the treatment of all DENV serotypes infection. An inhibitor that is targeting the α-GluII can be designed by using computational fragment-based approach. In this research, we constructed Tanimoto-based on 1-deoxynojirimycin (DNJ) fragment similarity and in vitro fragment libraries. The ligand for α-GluII inhibitors were designed by linking two potential fragments from these libraries. The result from molecular docking simulation showed that the ligand VG4 is the best inhibitor. Moreover, the simulation also showed the other seven ligands that designed in this research have a good binding affinity toward α-Glu II as well. Finally, computational pharmacological prediction and synthetic accessibility score also indicated the ligand VG4 and the selected ligands are potential to be developed as drug candidates for dengue therapeutics.