Diet is a modifiable key factor targeted in prevention and management of nonalcoholic fatty liver disease (NAFLD). The aim was to study the effect of Mediterranean Diet (MedDiet) on clinical, biochemical, and inflammatory profile in NAFLD patients with simple steatosis. Potential associations of signal transducer and activator of transcription 3 (STAT3) rs2293152 genotype to diet composition and patients' profile were investigated. In this nonrandomized, open-label, 24-week prospective intervention study, 44 untreated NAFLD patients with nonsignificant fibrosis received nutritional counsel to increase adherence to MedDiet. Adherence to MedDiet was estimated with MedDietScore. Furthermore, we genotyped STAT3 rs2293152 single nucleotide polymorphism and performed clinical and inflammatory measurements. In all patients, MedDietScore increased and anthropometric indices improved, whereas liver imaging, liver fibrosis score, blood pressure, fasting glucose, glycated hemoglobin (HbA1c), C-reactive protein (CRP), visfatin, and oxidized low-density lipoprotein levels were also significantly ameliorated compared with baseline (P < .05). No association of STAT3 polymorphism with diet composition was found. Comparisons of mean differences between G- and C-carriers at the end point of the trial showed that only visfatin was significantly associated with the STAT3 genotype (-0.0 ± 4.6 vs. -4.2 ± 3.9, P = .04, respectively). Carrying the G-allele was associated with an increase of the visfatin levels (3.4 ± 1.5 ng/mL, P = .028). Our results show amelioration of clinical, biochemical, and inflammatory biomarkers in NAFLD patients in response to MedDiet. STAT3 rs2293152 G-carriers experienced more beneficial changes at the end of the intervention compared with baseline. An association between visfatin levels and STAT3 genotype has been shown for the first time.