Childhood obesity is associated with stress. However, most treatment strategies include only dietary and physical activity approaches. Mindfulness may assist in weight reduction, but its effectiveness is unclear. We assessed the effect of mindfulness on stress, appetite regulators, and weight of children with obesity and anxiety. A clinical study was conducted in a pediatric hospital. Eligible children were 10–14 years old, BMI ≥95th percentile, Spence anxiety score ≥55, and who were not taking any medication or supplementation. Participants were assigned to receive an 8-week conventional nutritional intervention (CNI) or an 8-week mindfulness-based intervention plus CNI (MND-CNI). Anthropometry, body composition, leptin, insulin, ghrelin, cortisol, and Spence scores were measured at baseline and at the end of the intervention. Anthropometry was analyzed again 8 weeks after concluding interventions. Log-transformed and delta values were calculated for analysis. Thirty-three MND-CNI and 12 CNI children finished interventions; 17 MND-CNI children accomplished 16 weeks. At the end of the intervention, significant reductions in anxiety score (−6.21 ± 1.10), BMI (−0.45 ± 1.2 kg/m2), body fat (−1.28 ± 0.25%), ghrelin (−0.71 ± 0.37 pg/mL), and serum cortisol (−1.42 ± 0.94 µg/dL) were observed in MND-CNI children. Changes in anxiety score, ghrelin, and cortisol were different between groups (P < 0.05). Children who completed 16 weeks decreased BMI after intervention (−0.944 ± 0.20 kg/m2, P < 0.001) and remained lower 8 weeks later (−0.706 ± 0.19 kg/m2, P = 0.001). We concluded that mindfulness is a promising tool as an adjunctive therapy for childhood obesity. However, our findings need confirmation in a larger sample population.