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Peltophorum africanum (Fabaceae) is a deciduous tree widespread in southern Africa. The plant has many ethnomedical and ethnoveterinary uses. Root and bark decoctions are used to treat diarrhoea, dysentery, sore throat, wounds, back and joint pains, HIV-AIDS, venereal diseases and infertility. Pastoralists and rural farmers use the root and bark extracts to treat diarrhoea, dysentery, infertility, and to promote well-being and resistance to diseases in cattle. To evaluate these ethnobotanical leads, dried leaves, stem bark and root bark were extracted with ethanol, acetone, dichloromethane and hexane. Polyphenols in the extract were determined by the Folin-Ciocalteu method with gallic acid as standard. Qualitative antioxidant activity was screened by spraying thin layer chromatograms (TLC) of the extracts with 0.2% 1,1-diphenyl-2-picryl hydrazyl (DPPH), and quantified with Trolox equivalent antioxidant capacity (TEAC) assay. Minimum inhibitory concentration (MIC) and total antibacterial activity (TAA) were determined by serial microplate dilution for Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Enterococcus faecalis, with gentamicin as standard and tetrazolium violet as growth indicator. Acetone and ethanol extracted the largest quantity of material. Polyphenols concentration was 49.2% in acetone extract of the root and 3.8% in dichloromethane extract of the leaf. Antioxidant activity of at least 5 antioxidant compounds as measured by TEAC ranged from 1.34 (ethanol extract of the root) to 0.01 (hexane extract of the leaf). The total antibacterial activity (volume to which active compounds present in 1 g plant material can be diluted and still inhibit bacterial growth) was 1263 ml/g for ethanol extract of the root against S. aureus, and 800 ml/g for acetone extract of the root against P. aeruginosa. There was substantial activity against both Gram-positive and Gram-negative bacteria, with MIC values of 0.08 mg/ml for S. aureus and 0.16 mg/ml for P. aeruginosa. There is therefore a rationale for the traditional use of root and bark of P. africanum in treating bacterial infection related diseases.