A high-fat fast-food meal negatively impacts postprandial metabolism even in healthy young people. In experimental studies, epigallocatechin-3-gallate (EGCG), a bioactive compound present in green tea, has been described as a potent natural inhibitor of fatty acid synthase. Thus, we sought to evaluate the effects of acute EGCG supplementation on postprandial lipid profile, glucose, and insulin levels following a high-fat fast-food meal. Fourteen healthy young women 21 ± 1 years and body mass index 21.4 ± 0.41 kg/m2 were enrolled in a randomized, double-blind, placebo-controlled crossover study. Participants ingested capsules containing 800 mg EGCG or placebo immediately before a typical fast-food meal rich in saturated fatty acids. Blood samples were collected at baseline and then at 90 and 120 min after the meal. The EGCG treatment attenuated postprandial triglycerides ( p = 0.029) and decreased high-density lipoprotein cholesterol (HDL-c) ( p = 0.016) at 120 min. No treatment × time interaction was found for total cholesterol, low-density lipoprotein (LDL-c), and glucose or insulin levels. The incremental area under the curve (iAUC) for glucose was decreased by EGCG treatment ( p < 0.05). No difference was observed in the iAUC for triglycerides and HDL-c. In healthy young women, acute EGCG supplementation attenuated postprandial triglycerides and glucose but negatively impacted HDL-c following a fast-food meal.