As mango leaf tea contains mangiferin and other bioactive compounds, this study investigated its anti-inflammatory, antioxidant and hepatoprotective effects on rats with high-fat induced obesity. Three groups were established: a control group (AIN93M diet), an obese group (high-fat diet HFD) and a treatment group (HFD with mango leaf tea for 8 weeks). Mango leaf tea increased antioxidant enzymes, total antioxidant capacity, AdipoR2 and PPAR-α mRNA and proteins expressions and, it also inhibited the NF-κB p65 and SREBP1c genes expressions in the liver. This beverage also leads to Cpt1 overexpression and a significant decrease in the accumulation of fat droplets, improving the hepatic steatosis. Molecular docking suggested a positive interaction between mangiferin, the main bioactive compound of mango leaf tea, and PPAR-α. Mango leaf tea exhibited a hepatoprotective effect through activating PPARα and decreasing the NF-κB p65 expressions, reducing oxidative stress and steatosis, and improving the lipid metabolism.