Medemia argun (MA) is a relatively unknown species of fan palm that has been reported to possess antioxidant properties. This study explored the effect of Medemia argun seed extract on mice with lipopolysaccharide (LPS)-induced sepsis, using albino mice as the experimental model. The animals were divided into three groups of five. One group received alpha-lipoic acid (ALA) as a standard anti-septic drug, another group was treated with MA seed extract in five consecutive doses administered every other day, and the final group served as the positive control. As expected, LPS exposure significantly elevated serum inflammatory markers. However, treatment with MA seed extract or ALA resulted in a marked reduction in serum pro-inflammatory cytokines (TNF-alpha, IL1B, and IL6) and improved liver function parameters (AST, ALP, and TB) compared to the LPS-positive control group. Although ALT levels increased noticeably in the LPS-only group, they showed a modest reduction in the treated groups. Additionally, MA seed extract protected the mice against elevated serum nitric oxide levels and liver DNA damage, as indicated by the comet assay. Histological analysis also revealed significant improvement in liver tissue inflammation in the MA-treated animals compared to the LPS-only group. Collectively, these findings demonstrate the hepatic protective and anti-inflammatory effects of MA extract in this experimental model.