Abstract The effects and the prescription parameters of therapeutic exercise are not clear. For this reason, is needed to determine the effect of neuromuscular exercise on balance, muscle strength and flexibility specifying the parameters and characteristics of effective interventions in children between 6 and 12 years and adolescent between 13 and 18 years with Down Syndrome. The present study is a systematic review of effectiveness outcomes balance, muscle strength and flexibility in this population. The databases of PubMed, PEDro, EMBASE, SCIELO, Lilacs, Cochrane library were searched from May to December 2021. We recruited randomized controlled trials (RCTs) which met the inclusion criteria in our study. Ten studies were included. The interventions included mechanotherapy, vibration, and use of different unstable surfaces. The exercise frequency ranged from 3 to 5 days a week, and the duration of each session was between six and 15 min. The frequency was between two and three times a week for 6 and 12 weeks and the intensity were between 60 and 80% of maximal voluntary contraction. Neuromuscular exercise in different modes of application was associated with increases in chest and lower limb muscle strength mean 8.51, CI [2.35–14.67] kg and (21.54 [1.64, 41.43]) kg. Balance also improved when the mode of application was isokinetic training and core stability exercises (− 0.20 [− 0.29, − 0.12]) evaluated with stability index. Neuromuscular exercise appears to be effective for the improvement of both lower limb and chest muscle strength and balance in children over 8 years. No evidence was found in children under 8 years.