Hyperlipidemia, a major risk factor for cardiovascular diseases, is characterized by elevated blood lipid levels. Preliminary phytochemical investigation of Gomphrena celosioides leaf reveals the presence of resin, carboxylic acid, steroids, saponin, and alkaloids, which may contribute to its anti-hyperlipidemic activity. The evaluation of Gomphrena celosioides leaf extract's anti-hyperlipidemic activity against high-fat diet-induced hyperlipidemia showed promising results Gomphrena celosioides, a plant with potential bioactive compounds, was evaluated in a study involving five groups of animals: Group-1 Control (normal diet), Group-2 Negative Control (high-fat diet), Group-3 Positive Control (high-fat diet + Orlistat 10mg/kg), Group-4 (high-fat diet + Gomphrena celosioides leaf extract 100mg/kg), and Group-5 (high-fat diet + Gomphrena celosioides leaf extract 200mg/kg). The high-fat diet significantly elevated lipid parameters in the Group-2 (Negative Control). However, treatment with Gomphrena celosioides leaf extract (100mg/kg and 200mg/kg) significantly reduced total cholesterol, triglycerides, LDL and VLDL cholesterol, while increasing HDL cholesterol levels in a dose-dependent manner. The extract's efficacy was comparable to the standard anti-hyperlipidemic drug Orlistat (10mg/kg). Possible mechanisms of action include the inhibition of cholesterol absorption, suppression of hepatic lipid synthesis, enhancement of lipoprotein lipase activity, and antioxidant effects that reduce oxidative stress and inflammation, suggesting its potential as a natural therapeutic agent for managing lipid profiles. Biochemical analysis of serum samples suggests that the ethanolic extract of Gomphrena celosoides has a dose-dependent protective effect on liver function, as reflected in the significant changes in the levels of Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST). The histological results indicate that the ethanolic extract of Gomphrena celosoides can also possess hepatoprotective properties, particularly in the context of high-fat diet-induced liver damage. The study's findings indicate that Gomphrena celosioides leaf extract could be a valuable adjunct in managing hyperlipidemia.