Background/Objectives: Physical activity is generally recommended, but youth with disabilities present increased sedentary behaviors. This is often due to limited or inaccessible exercise options. The aim of this systematic review was to report on the state of knowledge about the role of adapted physical activity (APA) in improving gross motor performance (query 1), participation and QoL (query 2) of children and adolescents with neurological motor disability. Methods: Pubmed, Scopus and Cinahl databases were enquired in October 2023 and updated in May 2025. Inclusion criteria were the following: any type of physical activity; pediatric subjects with any neuromotor disease; and any type of outcome measure regarding gross motor performance, participation or QoL. The risk of bias (RoB) was assessed by means of ROB 2, Robins-I and JBI tools. Results were synthetized focusing on the outcome measures and the type of activity proposed. Results: Thirteen and seven studies were included relative to queries 1 and 2, respectively. They all were RCTs, and some presented randomization RoB. Several types of APA (e.g., resistance, high-intensity circuit, running, cycling, aquatic and dance training) and of outcome measures were enquired, mostly focusing on subjects with cerebral palsy or Down syndrome. An increased time of moderate-to-vigorous physical activity, improvement in timed functional tests, muscle strength and stability were observed. Conclusions: APA may improve functioning, social participation and promote active lifestyle in pediatric persons with neuromotor disabilities, without adverse effects. In the future, more specific indications based on the functioning profile are advisable to orient professionals to define individualized safe training programs.