Abstract: Background and Objective: Acokanthera oblongifolia is an evergreen medicinal shrub used for snakebites, itches, wounds and internal worms and the relief of itchy conditions and other skin disorders by the Mpondo and Xhosa tribes in South Africa. The objective of this study was to investigate the efficacy of the plant extracts against selected pathogens that cause human skin disorders and evaluation of the antioxidant capability for validation of folk uses of the plant. Materials and Methods: The agar diffusion and micro-dilution methods were used to determine the antimicrobial activities of the extracts against selected bacteria and fungi. The data were subjected to one way analysis of variance (ANOVA) and Duncan’s Multiple Range Test (DMRT) was used to determine significant differences (p<0.05) among treatment means. Results: The highest antibacterial activity (inhibition zone diameter >19 mm) was obtained with the acetone extract against Pseudomonas aeruginosa, Shigella sonnei, Shigella flexneri, Bacillus cereus, Streptococcus pyogens and Bacillus subtilis; by the ethanol extract against B. cereus. None of the extracts was active against the tested fungi, apart from the acetone extract which showed strong inhibitory activity against Candida glabrata. The ethanol extract showed a higher ABTS scavenging than those of gallic acid and BHT at concentrations lower than 0.15 mg mL–1. Conclusion: The in vitro antibacterial activity of the acetone extract of A. oblongifolia against the tested pathogens has provide scientific evidence to justify the ethnomedicinal use of A. oblongofolia against skin disorders in the study area and also indicate that the plant is a potential source for the development of antimicrobial and antioxidant agents.