A tick-borne, multisystemic disease, Lyme borreliosis caused by the spirochete Borrelia burgdorferi has grown into a major public health problem during the last 10 years. The primary treatment for chronic Lyme disease is administration of various antibiotics. However, relapse often occurs when antibiotic treatment is discontinued. One possible explanation for this is that B. burgdorferi become resistant to antibiotic treatment, by converting from their vegetative spirochete form into different round bodies and/or into biofilmlike colonies. There is an urgent need to find novel therapeutic agents that can eliminate all these different morphologies of B. burgdorferi. In this study, two herbal extracts, Samento and Banderol, as well as doxycycline (one of the primary antibiotics for Lyme disease treatment) were tested for their in vitro effectiveness on several of the different morphological forms of B. burgdorferi (spirochetes, round bodies, and biofilmlike colonies) using fluorescent, darkfield microscopic, and BacLight viability staining methods. Our results demonstrated that both herbal agents, but not doxycycline, had very significant effects on all forms of B. burgdorferi, especially when used in combination, suggesting that herbal agents could provide an effective therapeutic approach for Lyme disease patients.