Picralima nitida has a wide range of application in Africa traditional medicine. This research was designed to comparatively evaluate the bioactive constituents, antioxidant, and antimalarial potentials of leaves and stem bark of Picralima nitida. The plant’s leaves and stem bark were successfully extracted with methanol using cold extraction technique. The determination of the chemical constituents, antioxidant and antimalarial potentials were investigated using already established methods. The phytochemicals discovered in the leaves and stem bark include alkaloids, saponins, terpenoids, flavonoids, reducing sugar, tannins, phenolic compounds, glycosides, proteins and carbohydrates. The GC-MS analysis revealed 3-O-methyl-d-glucose (70.56%), phytol (5.67%), and hexanoic acid, 2 ethyl hexyl ester (13.93%), as the major components of the leaf extract while dodecanoic acid (18.34%), 9 octadecanoic acid (7.49%) and n-hexadecanoic acid (5.95%) were revealed as the stem bark extract’s chief components. The antioxidant potential at 200, 100, 50, 20, 10, 5, 2 and 1 µg/mL gave an IC50 of 2.08 ± 1.28, 14.76 ± 10.64 and 12.48 ± 9.66 µg/mL for standard, leaf extract and stem bark extract respectively. In the in vivo anti-malarial activity, a maximum average parasitaemia suppression of 47.00 ± 5.57 and 53.34 ± 3.63 % was observed at 800 mg/kg, for the leaf extract and the stem bark extract correspondingly. The stem bark extract showed a higher average chemo-suppression compared to the leaves extract. By this study, the use of P. nitida in the treatment of malaria and other ailments associated with oxidative stress is validated.