Background/Objectives: Natural bioactive compounds are promising interventions for obesity-related metabolic dysfunction. Lutein, a xanthophyll carotenoid with antioxidant and anti-inflammatory properties, may improve metabolic health, but its effects on liver function and gut microbiota in high-fat diet (HFD)-induced obesity are not fully elucidated. This study evaluated the effects of lutein supplementation on hepatic function, oxidative status, lipid metabolism, and gut microbiota composition in HFD-fed mice. Methods: Male C57BL/6J mice (6 weeks old) were randomly assigned to four groups (n = 8/group): Ctrl (low-fat diet), model (HFD), low-dose lutein (50 mg/kg/day), and high-dose lutein (100 mg/kg/day). Results: Following a 70-day intervention, lutein supplementation, particularly at the higher dose, reduced the liver index, improved serum lipid profiles, liver injury markers, and hepatic antioxidant capacity by increasing superoxide dismutase, catalase, and glutathione levels while reducing malondialdehyde content, and alleviated hepatic histopathological alterations. Lutein supplementation was also linked to elevated gut microbial richness and shifts in the relative frequency of several bacterial taxa, including partial restoration of Bacteroidota and enrichment of Roseburia and Faecalibaculum. These findings demonstrate that lutein supplementation attenuated HFD-induced metabolic and hepatic alterations, accompanied by improved antioxidant status and modulation of gut microbiota. Conclusions: Overall, lutein alleviated hepatic steatosis, oxidative stress, and metabolic dysfunction, highlighting its potential as a dietary strategy for managing obesity-related liver functions and gut dysbiosis.

High-fat diets (HFDs) can induce oxidative stress and gut microbiota imbalance, highlighting the need to explore functional dietary lipids such as red palm oil (RPO) for metabolic health improvement. This study investigated the effects of RPO intervention administered through oral gavage on growth performance, serum lipid profile, hepatic antioxidant capacity, and gut microbiota in HFD-fed mice. Compared to the high-fat control (HO) group, RPO treatment significantly reduced triglycerides (TG) and total cholesterol (TC), and increased high-density lipoprotein cholesterol (HDL-C). Furthermore, hepatic antioxidant capacity was markedly enhanced, as evidenced by improved superoxide dismutase (SOD) and catalase (CAT) activities and decreased malondialdehyde (MDA) levels in the HFD group receiving RPO. Moreover, RPO supplementation reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and attenuated hepatic steatosis. Gut microbiota analysis showed that RPO administration enhanced the relative abundance of beneficial bacteria while reducing potentially harmful taxa. Overall, these findings demonstrate that oral gavage of RPO can effectively alleviate HFD-induced metabolic disturbances by improving lipid metabolism, enhancing hepatic antioxidant defenses, and modulating gut microbial composition.