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It is a validated target of the antifolate drug pyrimethamine (Pyr) in <jats:italic>Plasmodium falciparum<\/jats:italic> (<jats:italic>Pf<\/jats:italic>), but its clinical efficacy has been hampered due to the emergence of drug resistance. This has made the attempt to screen Food &amp; Drug Administration\u2010approved drugs against wild\u2010 and mutant\u00a0<jats:italic>Pf<\/jats:italic>DHFR by employing an in\u2010silico pipeline to identify potent candidates. The current study has followed a virtual screening approach for identifying potential DHFR inhibitors from DrugBank database, based on a structure similarity search of candidates, followed by absorption, distribution, metabolism, and excretion estimation. The screened drugs were subjected to various parameters like docking, molecular mechanics with generalized born and surface area solvation calculations, and molecular simulations. 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