Hematopoietic stem cell transplantation (HSCT) is a treatment that requires long periods of hospitalization. The mobility restrictions result in physical, functional and psychological impairments. Physical exercise is a therapy that can restore physical and functional capacities; however, it is necessary to understand the effects of its practice in post-HSCT individuals. The purpose of this systematic review (SR) was to assess the impact of physical exercise in children and adolescents undergoing HSCT. The SR was conducted following the PRISMA guidelines through search in the electronic databases Embase, Lilacs, PEDro, PubMed and SCOPUS, without limitation of dates and languages. Randomized or non-randomized clinical trials with children and adolescents who underwent HSCT, aged between 3 to 19 years old, who participated in a regular physical activity program, were assessed. After removing duplicates and selecting studies according to the eligibility criteria, seven parallel studies incorporating hospitalized and discharged participants undertaking aerobic and strengthening exercises were included in this study. The main outcomes analyzed were exercise capacity, quality-of-life, body composition and freedom. Five studies comprised the meta-analysis regarding the effects of the distance walked in the 6-min walk test and quality-of-life. Physical exercise is considered to be safe, feasible and efficacious to prevent the decline of the quality-of-life in children and adolescents undergoing HCST, as well as a considerable improvement in physical capacity.