Background: Parkia biglobosa leaf has popular ethnomedicinal use in tropical Africa. However, little is known about its molecular biological effects. This study sought to investigate the in vitro antioxidant activity, angiotensin-Iconverting enzyme (ACE) inhibition and effects of aqueous-methanolic extract of P. biglobosa leaf (PBE) on mitochondrial membrane potential and reactive oxygen species (ROS) generation. Methods: Antioxidant activity was determined by extract's DPPH .(1,1-diphenyl-2-picrylhydrazyl radical), ABTS .+ [2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt radical cation] scavenging ability, reducing property and propensity to inhibit lipid peroxidation induced by prooxidants (FeSO 4 /sodium nitroprusside, SNP) in isolated rat tissue preparations. Determination of angiotensin-converting enzyme (ACE) inhibition was based on the hydrolysis of N-hippuryl-His-Leu hydrate (HHL) by the enzyme. Subsequently, the effects of PBE on toxicant-induced mitochondrial ROS formation and basal membrane potential (ΔΨm) were determined by 2′, 7′-dichlorodihydrofluorescin (DCFH) oxidation and safranine fluorescence respectively. Results: PBE significantly reduced ferric ions (P < 0.001), scavenged DPPH (EC 50 = 98.33 ± 1.0 μg/mL) and ABTS (EC 50 = 45.30 ± 0.1) radicals, with moderate Fe 2+ -chelating effect (40%). In rat liver and brain homogenates respectively, PBE prevented membrane peroxidation induced by FeSO 4 (EC 50 : 75.87 ± 2.1 μg/mL and 89.34 ± 2.5 μg/mL) and SNP (EC 50 : 28.10 ± 1.6 μg/mL and 17.25 ± 0.78 μg/mL). The extract's inhibition of ACE (IC 50 = 51.30 ± 5.1 μg/mL) and mild depolarization of isolated liver mitochondria membrane potential were concentration-dependent. Finally, PBE was more effective than catechin in attenuating calcium and SNP-induced surge in mitochondrial ROS generation. Conclusion: Parkia biglobosa leaf exhibits considerable ACE inhibitory effect, antioxidant activity and affects mitochondrial redox chemistry. These present findings also justify the ethnobotanical applications of the plant in the indigenous system of medicine.