Porphyromonas gingivalis (P. gingivalis) is capable of enhancing oral dysbiosis resulting in an imbalance between beneficial commensal and periodontal pathogenic bacteria that causes chronic inflammation. Nigella sativa (N. sativa) is a type of herbal plant with antioxidant, anti-inflammatory, antimicrobial, anticancer, and other properties. One of the main active ingredients is thymoquinone. Researchers conducted this research to determine the impact of using Nigella sativa as a component in the prevention or treatment of periodontal disease. This research included a lab experiment using a randomized post-test-only control group design. The animals used were male white Wistar rats (Rattus norvegicus), aged 10-11 weeks, and weighing approximately 150-170 grams. All of them received adaptation for a week. Afterward, 45 of them were randomly allocated into three research groups: control group C (LPS P. gingivalis), group E1 (N. sativa extract + LPS), and group E2 (LPS + N. sativa). The rats were terminated after 7, 14, and 21 days and immunohistochemistry was performed using monoclonal antibody anti-TLR-4 and monoclonal antibody anti-NF-kB. The results showed that TLR-4 and NF-κB increased in group C and decreased in E1 and E2 groups. Although it was not statistically significant, the TLR-4 and NF-kB expression decreased more in the E2 group than in the E1 group. The result of this research shows that Nigella sativa can reduce the expression of TLR-4 and NF-kB as a part of the host’s innate defense. Keywords: Nigella sativa, LPS Porphyromonas gingivalis, TLR-4, NF-kB, Periodontal disease