Many traditional herbal medicines are used by the Gurage and Silti peoples for treatment of various diseases. However, a lack of sound scientific data regarding traditional medicinal plant knowledge (TMPK) of the communities involved calls for the present study. We will therefore document the yet unexplored TMPK of the Gurage and Silti communities. Some of the traditional medicinal plants are supposed to have a strong antibacterial action. Therefore, the present study will further scientifically examine antimicrobial activity of the most-preferred claimed medicinal plants. The study will thus help to document the TMPK and provide the potential to identify medicinal plants which are most likely to be useful for the treatment of bacterial diseases.