Abstract Context Dipeptidyl peptidase 4 (DPP-4) metabolizes glucagon-like peptide-1 (GLP-1), and increased DPP4 levels are associated with obesity and visceral adiposity in adults. Objective Investigating DPP-4 levels in adolescents and their association with (1) circulating intact GLP-1 levels and glucose tolerance; (2) body mass index (BMI); and (3) visceral, subcutaneous, and liver fat compartments. Design Cross-sectional study, July 2012 to April 2015. Setting Pediatric obesity clinic, Uppsala University Hospital. Patients and Participants Children and adolescents with obesity (n = 59) and lean controls (n = 21) aged 8 to 18 years. Main Outcome Measures BMI SD score, fasting plasma concentrations of DPP-4, total and intact GLP-1, fasting and oral glucose tolerance test (OGTT) concentrations of glucose, and visceral adipose tissue (VAT) and subcutaneous adipose tissue volumes and liver fat fraction. Results Plasma DPP-4 levels decreased with age in both obese (41 ng/mL per year) and lean subjects (48 ng/mL per year). Plasma DPP-4 levels were higher in males in both the obesity and lean groups. With adjustments for age and sex, plasma DPP-4 level was negatively associated with intact GLP-1 at fasting (β = −12.3; 95% CI: −22.9, −1.8) and during OGTT (β = −12.1; 95% CI: −22.5, −1.7). No associations were found between DPP-4 and plasma glucose levels measured at fasting or after a 2-hour OGTT. Plasma DPP-4 level was 19% higher in obese subjects. Among adipose tissue compartments, the strongest association was with VAT (β = 0.05; 95% CI: −0.02, 0.12). Conclusions In adolescents, high plasma DPP-4 concentrations were associated with low proportions of intact GLP-1, high BMI, young age, and male sex. The observed associations are compatible with increased metabolism of GLP-1 in childhood obesity.