Onchocerca volvulus infection is a neglected public health disease that affects millions of people in the endemic regions of sub-Saharan Africa and Latin America. The disease is second to trachoma as the leading cause of blindness due to infection in the developing world and only few drugs are commonly used to treat nematode infections, creating a dangerous environment for the emergence of drug resistance. Through molecular docking simulations, 2,015 approved drugs were screened against two critical protein targets:  glutamate S-transferase and prolyl tRNA synthetase using Autodock-vina. The drugs’ interactions with the target proteins were analyzed using Discovery Studio Visualizer. Molecular dynamics was executed using Schrödinger LLC Desmond software.  The docking result showed the reference ligands GTX and HFG exhibiting a mean binding energy of – 5.77kcal/mol & -9.50kcal/mol, whereas all screened approved drugs demonstrated stronger binding, with affinities ranging from -6.60 to -7.0kcal/mol. The top-ranking compounds are Bedaquiline (-10.70 kcal/mol) and Telmisartan (-12.57 kcal/mol) showed the most favourable interactions. The Molecular dynamic results identified Diosmin, Azelastine and Adapalene as promising multi-target drugs based on their dynamic interactions (RMSD, RMSF, Protein-Ligand contacts and Radius of gyration) and potential to inhibit the Onchocerca volvulus targets. Additionally, other compounds like Drospirenone, Alectinib, Dutsteride and finasteride showed significant potential and warrant further investigation. The findings suggest that repurposing these drugs could provide an accessible and effective therapeutic option for onchocerciasis and broaden the range of treatment options. Further studies are recommended to validate the efficacy of these drugs against Onchocerciasis.