Microbial infections such as sexually transmitted infections (STIs) are very common in the Blouberg area. Due to the high cost of conventional medicine and the STI-related stigma, traditional medicine remains the main medical resource for most of the Blouberg community. Using a semi-structured questionnaire, ethnobotanical data was collected from 33 female traditional health practitioners that manage patients presenting with STIs. The determination of antimicrobial susceptibility of plant extracts was done using the broth micro-dilution assay against bacterial strain Neisseria gonorrhea and fungal strain Candida albicans. Results showed that 7 plant species were used to manage STIs such as gonorrhea, chlamydia and makgoma. Sexually transmitted infections were treated using Blepharis divesispina, Cyphostemma humile subsp. dolichopus, Drimia sanguinea, Harpogophytum procumbens, Jatropha erythropoda, Mokakutwane and Vachellia permixta. All of the tested extracts were inactive against N. gonorrhea at the highest concentration (12.5 mg/ml) with the exception of D. sanguinea. Only B. diversispina, C. humile subsp. dolichopus and V. permixta showed antimicrobial activity against C. albicans. These results may support anecdotal claims for the use of the selected plant species to treat venereal diseases.