Abstract: Background and Objective: Vachellia karroo is a forage plant for goats belonging to Fabaceae family, that is also used for the treatment of sexually transmitted infections in the Eastern Cape Province of South Africa. However, the pods from the tree are often discarded as waste causing environmental pollution. This study, therefore, aimed at evaluating the antimicrobial potentials of the pods towards minimizing their loss and negative impact on the environment. Materials and Methods: Antimicrobial evaluation of acetone, aqueous, hexane and methanol extracts of V. karroo pods using agar dilution assay was done. Eight bacterial strains and 6 fungal isolates were screened. Results: The results revealed that methanol extract had a broad-spectrum activity, with greater sensitivity against Gram-positive than Gram-negative strains. The extracts also showed great inhibition against Candida albicans the fungal isolate responsible for causing candidiasis in women. Conclusion: Since the pods showed a promising antimicrobial activity, they could serve as a cheap and ready source of antibiotic for the treatment and management of sexually transmitted infections, caused by these organisms.