Abstract: Background and Objective: Many plant-derived compounds have been used as drugs, either in their original or semi-synthetic forms. Plant derived metabolites can also serve as a lead compounds, which may be used as templates for the development of new drugs. Therefore, the aim of this study was to evaluate the antimicrobial activities of solvent fractions of Vernonia amygdalina shoot apex and Prunus africana bark against multidrug resistant bacterial strains. Materials and Methods: The plant materials were obtained through successive extractions using solvents of different polarity such as petroleum ether, chloroform, acetone and methanol. The antibacterial activities of the fractions were then evaluated by the hole-agar-well diffusion method. The minimum inhibitory concentration of the solvent fraction was determined against the isolated microorganism by agar dilution method. Then, the data were analyzed using Statistical Package for Social Science (SPSS) version 16. p<0.05 based on one-way ANOVA was used to indicate statistically significant differences. Results: All the Prunus africana bark solvent fractions showed antimicrobial activities which were found to exhibit significant antimicrobial activity differences among fractions against the clinical strains. The methanol extract demonstrated the strongest activities against the majority of clinical strains, whereas the acetone extract of Prunus aricana was the most effective with minimal inhibitory concentration of 0.65 mg mL–1 against Citrobacter fruindi and Staphylococcus pyogenes. On the other hand, the methanol extract of Vernonia amygdalina shoot apex, inhibited majority of strains at tested concentrations while other solvent fractions had limited antimicrobial activities. Conclusion: In general, Prunus africana extracts exhibited more antimicrobial activities than Vernonia amygdalina extracts. Comparatively, the methanol fraction of the plant showed the strongest antibacterial activities mainly against E. coli, C. koseri, E. aerogenes, S. aureus and E. cloacae clinical strains.