Childhood obesity is a major public health concern. We wanted to evaluate the effectiveness of a multidisciplinary program based on healthy eating, exercise, cognitive-behavioral therapy, and health education to achieve weight loss and improve metabolic parameters in overweight and obese children. A randomized, controlled clinical trial with long-term follow-up (24 months) was conducted at a community care center in overweight and obese individuals aged 6–12 years. A sample of 108 children was divided into an experimental and a control group receiving a standard care program. The experimental groups received a 12-month interdisciplinary program; the results were evaluated at 4 months, the end of the intervention, and at follow-up 12 months later. Anthropometric and biological marker measurements related to metabolic alterations, dyslipidemia (based on total cholesterol), hyperglycemia, fasting glycaemia, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in blood were recorded. The intervention had a significant effect ( p < 0.001) in terms of decreased body mass index, skinfolds, and waist and arm circumferences. These changes were accompanied by biochemical changes underlying an improvement in metabolic parameters, such as a significant reduction in total cholesterol, low-density lipoprotein-cholesterol, triglycerides, and hyperglycemia and a significant increase in high-density lipoprotein-cholesterol. These effects were still significant for markers of excess weight or obesity in the experimental group 12 months after the end of the intervention, suggesting that an enduring change in healthy lifestyles had been maintained period. This interdisciplinary, nurse-led program helped to reduce childhood and adolescent excess weight and obesity and had long-lasting effects.