Malaria remains the leading cause of deaths globally, despite significant advancement towards understanding its epidemiology and availability of multiple therapeutic interventions. Poor efficacy of the approved vaccine, and the rapid emergence of antimalarial drug resistance, warrants an urgent need to expedite the process of development of new lead molecules targeting malaria. Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes crucial for ribosomal protein synthesis and are valid antimalarial targets. This study explores the prospects of (re-)positioning the repertoire of approved drugs and natural products as potential malarial aaRS inhibitors. Molecular docking of these two sets of small-molecules to lysyl-, prolyl-, and tyrosyl-synthetases from Plasmodium followed by a comparison of the top-ranking docked compounds against human homologs facilitated identification of promising molecular scaffolds. Raltitrexed and Cefprozil, an anticancer drug and an antibiotic, respectively, showed stronger binding to Plasmodium aaRSs compared to human homologs with > 4 kcal/mol difference in the docking scores. Similarly, a difference of ~ 3 kcal/mol in Glide scores was observed for docked Calcipotriol, a drug used for psoriasis treatment, against the two lysyl-tRNA synthetases. Natural products such as Dihydroxanthohumol and Betmidin, having aromatic rings as a substructure, showed preferential docking to the purine binding pocket in Plasmodium tyrosyl-tRNA synthetase as evident from the calculated change in binding free energies. We present detailed analyses of the calculated intermolecular interaction for all top-scoring docked poses. Overall, this study provides a compelling foundation to design and develop specific antimalarials.