The aim of this research study was to examine the effects of Assisted Cycling Therapy (ACT) on adaptive/maladaptive behaviors, depression, and self-efficacy in adolescents with Down syndrome (DS). The participants were counterbalanced to either intervention groups of 1) Assisted Cycling Therapy (ACT), in which the participants' voluntary pedaling rates were augmented with a motor to ensure the maintenance of 80 rpm or greater 2) Voluntary Cycling (VC), in which participants cycled at their self-selected pedaling rate or 3) No Cycling (NC), in which the participants sat and watched a video. The ACT and VC groups exercised 3 days a week for 8 weeks for 30 min. Adaptive behavior was measured by the Vineland Adaptive Behavior Scale (VABS) II to analyze the changes in daily living skills and maladaptive behaviors, depression was measured by the Children's Depressive Inventory, and exercise perception and self-efficacy were measured by the PASE scale, pre and post interventions. The result of this study revealed that social coping skills (p = 0.001) and depression (p = 0.022) improved more after participating in ACT than VC or NC interventions. In addition, externalizing maladaptive behaviors (p = 0.023) improved pre and post ACT and VC interventions but not NC. Our results are discussed with respect to neurological mechanisms associated with our interventions and their effect on functioning in adolescents with DS.