Background: One of the most widely used insecticides, is alpha-cypermethrin (α-CYP). Excessive dependence on such insecticides leads to severe environmental pollution, negatively affecting human and animal health.

Aim: The goal of the current investigation based on utilizing Cyperus rotundus tuber non-polar extract, to assist reducing the deleterious impact of α-CYP on liver tissues of male albino rats.

Results: FT-IR analysis identified the most important active compounds present in the extract. While the active biochemical ones were confirmed by individualization and identification utilizing GC/MS. The results indicated that the most important active compounds in the hexane extract were oxygenated compounds,17-octadecynoic acid (60.51%) and 9-octadecenoic acid, methyl ester (6.54%) in addition to nitrogenated compounds, such as histidyl histidine (4.75 %). The results showed that the C. rotundus extract administration decreased liver enzymes; alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Also, it increased antioxidant; glutathione (GSH), superoxide dismutase (SOD) enzyme, decreased oxidant; malondialdehyde (MDA), and nitric oxide (NO). Furthermore, it decreased liver inflammatory markers; nuclear factor-κB (NF-κB), adiponectin, and lipocalin. Conclusion: Results indicated that C. rotundus hexane extract exerts a potent protective effect against α-CYP-induced oxidative damage and inflammation in rats' liver tissues.