Obesity is an important public health problem. The combined use of different therapies performed by an interdisciplinary group can improve the management of this health issue. The main goal of this research is to determine the effectiveness of a multidisciplinary program based on healthy eating, exercise, cognitive-behavioral therapy, and health education in improving metabolic comorbidity, Body Mass Index (BMI), and nutritional habits among obese adults, at short (12 months) and long term (24 months). A randomized controlled clinical trial was conducted at a community care center between February 2014 and February 2016. A random sampling was done (299), total population (3262). A sample of 74 subjects diagnosed with obesity (experimental group, n = 37 and control group, n = 37) was conducted. Inclusion criteria: obese people (BMI: >30 kg/m2) with metabolic comorbidity and bad nutritional habits. Exclusion criteria: other comorbidities. A 12-month interdisciplinary program (with pre-test, 12 months and 24 months of follow-up) was applied. Intervention is based on healthy eating, exercise, and cognitive behavioral therapy. The intervention had a positive effect on nutritional habits (F2;144 = 115.305; p < 0.001). The experimental group increased fruit and vegetable intake (F2;144 = 39.604, p < 0.001), as well as fortified foods (F2;144 = 10,076, p < 0.001) and reduced fats, oils, and sweets F2;144 = 24,086, p < 0.001). In the experimental group, a BMI reduction of 2.6 to 24 months was observed. At follow-up, no participant had inadequate nutritional habits, compared to 35.1% of the control group (χ22 = 33,398; p < 0.001). There was also a positive response of metabolic comorbidities in the intervention group. The interdisciplinary program improved all participants’ metabolic parameters, BMI, and nutritional habits while maintaining the long-term effects (24 months).