Children with ADHD face deficits in interference control due to abnormalities in brain structure. A low body mass index and high physical activity are factors promoting brain health and may have the potential to reduce ADHD-related cognitive deficits. We aimed to investigate the predictive values of ADHD, body mass index and physical activity for interference control and the potential mediation of these associations by brain structure.; At 9 and 11 years, 4576 children with ADHD and neurotypical peers from the ABCD-cohort completed a Flanker task, anthropometric assessments and reported physical activity. Additionally, T1- and T2-weighted magnet resonance images were collected at both measurement time points.; ADHD, lower physical activity and higher body mass index at baseline predicted lower interference control. Gray matter volume, surface area and gray-white matter ratio contributed to interference control. The longitudinal association between body mass index and interference control was mediated by gray-white-matter ratio. This mediating effect was stronger for children with ADHD than neurotypical peers and mainly restricted to regions associated with cognitive control.; The maintenance of a lower body mass index contributes to interference control by a tendency to normalize regional alterations in grey-white-matter ratio. Being compliant with physical activity also promises higher interference control, but brain structure does not seem to underlie this association.