Background: Combretum platypterum is used ethno-medically in the treatment many diseases in Africa, such as; helminthiasis, sexually transmitted diseases, conjunctivitis, malaria, lumps, fever, eye problems, diarrhea, lower backache, coughs, swellings, as febrifuge, tonic, and to stop post-partum bleeding. Aim: This work was aimed at investigating the phytochemical, proximate, anti malarial, anti inflammatory, anti bacterial and anti fungal activities of leaf extracts of Combretum platypterum. Methods: Leaves of C. platypterum were cold extracted with methanol, ethyl acetate and n-hexane. The extracts were subjected to preliminary phytochemical analyses, proximate, anti malarial, anti inflammatory and antimicrobial tests. Results: The results revealed that, alkaloids, terpenoids, flavonoids, cardiac glycosides, carbohydrates, resins and reducing sugars were found in all the extracts. It was also observed that the presence of the metabolites in each extract was in polarity-dependent manner. The percentage composition of carbohydrates was also the highest followed by the composition of proteins. The suppressions of the extracts against P. falciparum at half-maximal inhibitory concentration (IC50 mg/ml) were found to be higher than that of chloroquine at IC50 µg/ml. It was also found that methanol extract had the highest inhibition against Gram positive, Gram negative bacteria and C. albicans in a dose-dependent manner. K. pneumonia was resistant to the inhibition of the extracts. The anti inflammatory assays showed that methanol extracts at 500 mg/ml exhibited higher lipoxygenase Inhibition than diclofenac at 500 µg/ml. Ethyl acetate extract showed highest inhibition of heat-induced hemolysis, protein denaturation and proteinase among all the extracts. Conclusion: The therapeutic use of the leaves of C. platypterum against malaria and swelling was confirmed by the activities of the extracts against inflammation and P. falciparum. It is also necessary that the bioactive compounds responsible for these activities be isolated.