Down syndrome (DS) is related to diseases like congenital heart disease, obstructive sleep apnea, obesity and overweight. Studies focused on DS associated with obesity and overweight are still scarce. The main objective of this work was to analyze the relationship between dietary intervention, physical exercise and body composition, in DS with overweight and obesity. This review is based on the PRISMA guidelines (Preferred Reporting Items for Systematic reviews and Meta-Analyses). Selection criteria for this analysis were: publications between January 1997 and December 2019; DS individuals with overweight and obesity; clinical trials using dietary intervention and physical exercise paying attention to changes in body composition. Selected clinical trials were focused on an exclusive intervention based on physical exercise. The anthropometric measures analyzed were body fat, BMI, waist circumference, body weight and fat free mass. The main conclusion is that prescribing structured physical exercise intervention may be related to a greater variation in body composition. Despite limited number of clinical trials analyzed, it can be assumed that the reported studies have not achieved optimal results and that the design of future clinical trials should be improved. Some guidelines are proposed to contribute to the improvement of knowledge in this field.