The increased prevalence of malaria requires continuous efforts towards the discovery of natural antimalarial agents targeting important biochemical pathways of the parasite. The Plasmoduim falciparum lactate dehydrogenase (pfLDH) is a glycolytic enzyme whose critical roles and unique characteristics make it an efficient antimalarial target. The aim of this study was to employ in silico methods to identify potential inhibitors of pfLDH from the selected bioactive compounds of Combretaceae species. One hundred and fifty (150) Combretaceae compounds were screened using molecular docking analysis on Schrödinger Maestro 12.5, followed by pharmacophore modelling and ADMET (absorption, distribution, metabolism, excretion and toxicity) study of the highest affinity compounds. Myricetin 3-O-glucoside and 2''-O-Galloylisovitexin showed higher binding affinities (-13.413 Kcal/mol and -12.896 Kcal/mol respectively) for pfLDH compared with -10.400 Kcal/mol displayed by nicotinamide adenine dinucleotide (NADH) (the co-factor). They interacted with GLY27, GLY29, MET30, ILE31, ASP53, GLY99, THR101 and TYR247 at the NADH binding site of the enzyme. The pharmacophore modelling showed the involvement of aromatic rings and hydrogen bond donors and acceptors in the interactions of the compounds with the target. Hence, these compounds could be said to possess the structural features, binding affinities and molecular interactions required as inhibitors of pfLDH and could be developed into antimalarial drugs following lead optimisation and experimental studies.