BackgroundPeriodontitis, marked by deep periodontal pocket depth (PPD), facilitates bacterial colonization and inflammation, necessitating adjunctive therapies. Although 0.2 % chlorhexidine (CHX) mouthwash is effective, its side effects have led to the search for alternative treatments. Peperomia pellucida (L.) Kunth, known as Pepper Elder, is a traditional medicinal plant with potential as an adjunctive herbal therapy for periodontitis. ObjectiveThis study aimed to investigate the anti-inflammatory efficacy of Peperomia pellucida extract in rats with induced periodontitis. MethodsA post-test control group design was used in this laboratory experimental study. Four groups of Wistar strain Rattus norvegicus rats were utilized: a Pristine group (without periodontitis), a negative control group (induced periodontitis only), a positive control group (induced periodontitis and administered 0.2 % CHX), and an experimental group (induced periodontitis and administered 2.5 μL of Pepper Elder extract). Each treatment group received daily administration for one week. PPD measurements were taken on days 0, 3, 5, and 7. Blood serum was collected on day 7 for ELISA to measure IL-1β, TNF-α, IL-10, and IL-13 levels. Statistical analysis was performed using the Kruskal-Wallis test with a post hoc LSD and Mann-Whitney test. ResultsThe extract-treated rats showed a decrease in PPD, with significant differences between the extract group and the negative control group (p < 0.05). TNF-α levels in the extract group differed significantly from the negative control group (p < 0.05) but not from the Pristine and positive control groups. IL-1β levels differed significantly only from the negative control group. IL-10 levels were significantly different from both the Pristine and negative control groups, while IL-13 levels differed significantly only from the negative control group. ConclusionPeperomia pellucida (L.) Kunth extract exhibits anti-inflammatory effects in rats with induced periodontitis.