Background: Adults with fatty liver present unusual glycaemia and lipid metabolism; as a result, non-alcoholic fatty liver disease (NAFLD) is now considered as part of the metabolic syndrome (MetS). Objective: To assess the 6- and 12-month effects of customized hypocaloric dietary and enhanced physical activity intervention on intrahepatic fat contents and progression of NAFLD, in patients with MetS. Design: Cross-sectional study in 155 participants (40-60 years old) from Balearic Islands and Navarra (Spain) with a diagnosis of NAFLD and MetS, and BMI (body mass index) between 27 and 40 kg/m(2); patients were randomized in a 1:1:1 ratio to either Conventional Diet, Mediterranean diet (MD)-high meal frequency, and MD-physical activity groups. Methods: Dietary intake was assessed using a validated food frequency questionnaire. Adherence to Mediterranean diet, anthropometrics, physical activity, and biochemical parameters (fasting glucose, glycated hemoglobin, bilirubin, aspartate aminotransferase, alanine aminotransferase-ALT-, gamma-glutamyl transferase, uric acid, urea, creatinine, albumin, total cholesterol, high-density lipoprotein cholesterol-HDL-cholesterol-, and triglycerides) were also assessed. Results: Subjects with NAFLD and MetS had reduced intrahepatic fat contents, and liver stiffness, despite the intervention the participants went through. All participants ameliorated BMI, insulin, Hb1Ac, diastolic blood pressure, HDL-cholesterol, and ALT, and improved consumption of total energy, fish, and legumes. Participants in the MD-HMF group improved waist circumference. Conclusions: Customized hypocaloric dietary and enhanced physical activity interventions may be useful to ameliorate NAFLD.