The study was designed to investigate the effect of lycopene, hesperidin, and essential oil and their nano-formulation form in high-fat diet (HFD) -induced obese Wistar rats. To achieve this, a total of ninety adult Wistar male rats were used. The animals were made obese by feeding rats' high-fat diet (HFD, cholesterol, and bile acid). A dose of cholesterol (30 mg/0.3 mL olive oil /1 kg b.w.) was orally administrated (five times per week ) for 8 consecutive weeks. Obesity was confirmed by the percentages of body weight gain. Animals were divided into negative control groups (normal rats received normal diet) and positive control groups (normal rats received HFD ) and treatment groups (obese rats received different samples) of five animals each. Dose of lycopene and its nanoparticles 50 mg/kg b. wt., hesperidin, essential oil, and their nano-formulation form (100 mg/kg b.wt). All samples and standard drug (orlistat 12 mg/kg b. wt.) were orally administered once daily for four weeks. At the end of experiement, all animal groups were sacrificed and blood samples were collected. Different parameters including total cholesterol, triglycride, HDL-cholesterol, total lipid, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatinene and urea were determined in the serum. The liver tissue was excised for the determination of hepatic antioxidant biomarkers (catalase and GSH) and oxidative stress (lipid peroxide). Histopathological examination of liver tissue of obese rats showed diffuse fatty liver, circumscribed hepatic vacuoles with prepheralnucleous. However, obese rats- treated with all different samples declaring amelioration in all the measured parameters. The results obtained illustrated that the nano-formulation form are more effective than a native form of lycopene, hesperidin, and essential oil. Besides, the lycopene and its nanoparticles were more effective than hesperidin, essential oil, and their nano-formulation forms. So, it could be concluded that , oral supplementation with lycopene, hesperidin, essential oil, and their relative nano-formulation forms can treat hepatic dysfunction in obese rats.