Many oral pathogens are implicated in the periodontal diseases. Strategies such as eliminating local microbial load are effective in preventing the progression of the periodontal disease. Many herbal/medicinal plants are known for their antibacterial properties. Fermentation of herbal plants with lactic acid bacteria has known to enhance various bio-active properties, thus the study aimed to investigate the effect of a herbal preparation fermented with Lactobacillus reuteri LR107 in in vitro antibacterial assays and in the experimental periodontal disease. The antibacterial activities were first compared in fermented and non-fermented herbal preparation. Fermented herbal preparation demonstrated a wide-spectrum anti-microbial activity to seven oral pathogens. HPLC and NMR studies further identified the major bioactive markers in the fermented herbal preparation to be berberine and palmatine. Lastly, ligation-induced periodontitis model is used to evaluate the in vivo effect of the fermented herbal preparation. Alveolar bone loss by the preparation was inhibited to a degree similar to that by the doxycycline control. The fermented herbal preparation demonstrated antibacterial activities and preserved alveolar bone resorption in experimental periodontitis.