Weight gain and metabolic disruptions are common in children and adolescents treated with antipsychotics, but the underlying mechanisms are unclear, complicating prevention and treatment. This study examines the impact of risperidone on appetite-regulating hormones (insulin, leptin, bioleptin) and their relationship to body weight changes over time. In a post-hoc analysis, we evaluated the correlation of appetite-regulating hormones with BMI z-scores during treatment and at a 6-month follow-up. The sample consisted of 10 participants (80% male, median age 9.7 years). A significant increase in bioleptin (p < 0.05) and BMI z-scores was observed over the 6 months. Initially, HOMA-IR, insulin, leptin, and bioleptin were significantly associated with BMI z-scores, but this association diminished after 6 months of treatment. Additionally, higher risperidone exposure correlated with lower appetite-regulating hormones at the 6-month mark. These findings indicate that risperidone significantly affects appetite-regulating hormones in children and adolescents, potentially contributing to antipsychotic-induced weight gain.