Background and aim: Several studies have shown that the optimum lime peel has antibacterial power to bacteria. Higher concentrations of flavonoids are found in the lime peel compared to other parts such as seeds, fruit, and juice. The aim of this study was to determine the lime peel extract effects in decreasing the levels of interleukin 6 in mice infected with Salmonella typhi. Materials and methods: This study is a true experimental pre-post test design to investigate the effect of lime peel extract (LPE) on serum level of IL-6. Mice were divided into: group I (LPE 510 mg/kg/bw), group II (LPE 750 mg/kg/bw), positive control and negative control. The intervention was carried out for 5 days. After the fifth day, mice were maintained for 3 weeks to determine the serum level of IL-6. Results: The results of phytochemical screening prove that lime peel contains flavonoids, tannins, saponins, alkaloids, and triterpenoids. Intervention of lime peel extract for 5 days reduced IL-6 levels in the LPE510 group by 19.63 pg/mL (p=0.003), and in the LPE750 group by 24.53 pg/mL (p=0.002). Conclusion: LPE (510 and 750 mg/kg/bw) significantly decreases serum levels of IL-6. Lime peel extract as a traditional plant can be used as adjuvant therapy in reducing proinflammatory factors in Salmonella typhi infections.