The effects and the prescription parameters of therapeutic exercise are not clear. For this reason, is needed to determine the effect of therapeutic exercises on the motor function of children with Down Syndrome (DS) aged 0 to 3 years. The present study is systematic review and meta-analysis of effectiveness outcomes in this population: gait, balance, motor development, fine motor skills, and executive functions. The databases of PubMed, PEDro, EMBASE, SCIELO, Lilacs, Cochrane library were searched from January to December 2019. We recruited Randomized Controlled Trials (RCTs) which met the inclusion criteria in our study. Six studies and 151 participants were included. Two types of therapeutic exercises, aerobic and neuromuscular, were identified. Both types of exercise were effective in improving outcomes. There were no differences between the modes of application of the exercise. No differences were identified between the treadmill and the physiotherapy plan for the reduction of the time to reach independent walking, Mean Difference (MD) 46.79, 95% Confidence Interval (IC) (− 32.60, 126.19), nor for the increase in walking speed MD 0.10 IC (− 0.02, 0.21) m/s. This study suggests that aerobic exercise therapy has a potentially effective role to promote the gait and motor development of children with DS aged 0 to 3 years when it is applied using a treadmill with a frequency of 5 days, a duration of 6–8 min, and an intensity of between 0.2 and 0.5 m/s. Studies with less heterogeneity and larger sample sizes are required.