This study examines cognitive and motor function in adolescents with Down syndrome (DS) following an 8-week assisted cycling therapy intervention. Forty-four participants were randomly assigned to three groups consisting of an assisted cycling (AC) (i.e., exercise accomplished through the use of a motor), a voluntary cycling (VC) (self-selected cadence), and a no cycling (NC) control group. Both ACT and VC groups rode a stationary bicycle for three 30-minute sessions a week, for a total of eight weeks. Participants completed cognitive testing that assessed information processing and manual dexterity at the beginning and at the end of the 8-week intervention. Consistent with our hypothesis, the results showed that information processing and manual dexterity improved following 8 weeks of cycling for the ACT group. These results were not seen for individuals in the voluntary and non-exercise groups. Our results suggest that assisted cycling therapy may induce permanent changes in the prefrontal cortex in adolescents with DS.