Objectives and Study: Salicylic acid (SA), a phenolic compound produced by plants, may play a beneficial role on health. A pilot study showed that children with obesity had lower serum SA than normal-weight children. The aim of this trial was to evaluate the effect of a 1-year nutritional–behavioral intervention on serum SA levels and to study a possible association between SA levels and metabolic profile changes in children with obesity. Methods: This was an interventional longitudinal observational uncontrolled cohort study. Forty-nine children with obesity, aged >6 years were evaluated. BMI (body mass index) z-scores were calculated. Fasting blood samples were analyzed for lipids, insulin, and glucose. The most significant metabolic variables were calculated. Serum SA was measured using a gas chromatography–mass spectrometry method. The 1-year intervention was based on the promotion of a balanced and normocaloric diet, in accordance with the national guidelines for treatment of childhood obesity. Additionally, behavioral education, based on the revised CALO-RE (Coventry, Aberdeen, and London-REfined) taxonomy, was performed. Results: At the end of intervention, children showed an increase in serum SA levels (mean (Standard Deviation, SD) 0.06 (0.02) vs. 0.09 (0.05) µmol/L; p < 0.001), a reduction of BMI z-score (3.14 (0.79) vs. 3.02 (0.82); p < 0.001), TyG index (4.52 (0.20) vs. 4.48 (0.23); p < 0.001), AIP (atherogenic index of plasma) (0.36 (0.21) vs. 0.27 (0.25); p < 0.001), and triglycerides/HDL (high density lipoprotein) cholesterol (2.57 (1.28) vs. 2.18 (1.22); p < 0.001) ratio. No statistically significant change in HOMA-IR (homeostasis model assessment index) was observed (4.20 (3.29) vs. 4.03 (2.28)). An association between the longitudinal variation of serum SA and HOMA-IR was found (correlation coefficient: −0.338, p = 0.02). Conclusion: Nutritional–behavioral intervention may improve the circulating SA and the metabolic profile in children with obesity. Serum SA could influence mainly glucose metabolism. Further larger studies are needed to evaluate whether a nutritional intervention based on specific advice regarding the quantity and type of fruit and vegetables (FV) consumption could provide benefits in terms of metabolic syndrome.