Introduction. Periodontitis is a serious gum infection that disrupts the soft tissue around teeth. This study aimed to identify the most effective fraction of the Chinese medicine Kangfuxin for periodontitis treatment in a rat model. Material and methods. Kangfuxin solution was subjected to sequential extraction using chloroform, ethyl acetate, n-butanol, and water. The extracts were evaporated, dissolved in DMSO, diluted in water, and administered to rats via gavage (0.5 mL/day) for 2 weeks. The n-butanol extract was further fractionated using macroporous resin chromatography with 10%, 30%, 50%, 70%, and 90% ethanol elution. Levels of inflammatory cytokines IL-6, IL-1(3, and TNF-alpha in periodontitis samples were examined by ELISA. Leukocyte infiltration in the cementum was analysed by haematoxylin and eosin (H&E) staining. Results. The n-butanol extract showed the best anti-inflammatory effect, reducing IL-6, IL-1(3, and TNF-alpha levels in periodontitis samples and alleviating tissue damage and leukocyte infiltration in the cementum. Further fractionation revealed that the 50% ethanol fraction of the n-butanol extract had the most potent action in attenuating inflammation. This fraction suppressed the activation of the PI3K-AKT-mTOR signalling pathway in periodontitis samples. Application of a PI3K activator counteracted the anti-inflammatory effect of the 50% ethanol fraction. Conclusions. We identified a potent anti-inflammatory fraction (50% ethanol fraction of the n-butanol extract) of Kangfuxin for periodontitis treatment. This fraction suppressed the activity of the PI3K-AKT-mTOR signalling pathway in periodontitis samples. Further research is needed to isolate and characterise the specific bioactive compounds within this fraction.