Most of the frontline drugs being used to treat malaria are gradually losing efficacy due to parasite resistance and this stipulates that new antimalarial drugs are discovered and developed either from plant origin or synthesis this study employed computational techniques to investigate the potential of phytochemicals from a medicinal plant (Andrographis paniculata) to act as potential inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase (PfDHODH). In this study, the aerial parts of Andrographis paniculata were locally sourced and processed, and cold extraction was carried out using 100 % dichloromethane, ethyl acetate and methanol. The extracts were characterized using GC-MS analysis to identify the various phytochemicals present. Spectra analysis revealed the presence of secondary metabolites, majorly alkaloids and terpenoids. The GC-MS revealed 60 compounds which were docked against PfDHODH and screened using the known inhibitor, 5-methyl-7-(naphthalen-2-ylamino)-1H-{1,2,4}triazolo{1,5-a}pyrimidine-3,8-diium, DSM1, as reference. 16 compounds were selected for druglikeness and in-silico pharmacokinetic property prediction and these were submitted to the online server, Admetlab 2.0. Based on the druglikeness assessment (Quantitative Estimate of Druglikeness, QED), 6 of the compounds were found to possess druglike qualities and these six were alkaloids and terpenoids, including Andrographolide. After considering other Pharmacokinetic parameters such as absorption, distribution, metabolism and toxicity, 4 compounds were eventually selected as potential PfDHODH inhibitors with optimum pharmacokinetic properties that are worth considering as lead compounds for an antimalarial drug discovery effort. The four compounds identified are 6-methoxy-2-methyl-quinoline-3-carboxylic acid-2-dimethylamino-ethylester (MET24_671), Andrographolide (MET25_998), 1-(6-purinyl)-2-pyrolidinecarboxylic acid (DCM14_463) and 2-ethylacridine (EA24_614) of which DCM14_463 was deemed the best. © 2023 Wresdiyati et al.