Abstract Treadmill training (TT) has been extensively used as an intervention to improve gait and mobility in patients with Parkinson’s disease (PD). Regional and global effects on brain activity could be induced through TT. Training effects can lead to a beneficial shift of interregional connectivity towards a physiological range. The current work investigates the effects of TT on brain activity and connectivity during walking and at rest by using both functional near-infrared spectroscopy and functional magnetic resonance imaging. Nineteen PD patients (74.0 ± 6.59 years, 13 males, disease duration 10.45 ± 6.83 years) before and after 6 weeks of TT, along with 19 age-matched healthy controls were assessed. Interregional effective connectivity (EC) between cortical and subcortical regions were assessed and its interrelation to prefrontal cortex (PFC) activity. Support vector regression (SVR) on the resting-state ECs was used to predict prefrontal connectivity. In response to TT, EC analysis indicated modifications in the patients with PD towards the level of healthy controls during walking and at rest. SVR revealed cerebellum related connectivity patterns that were associated with the training effect on PFC. These findings suggest that the potential therapeutic effect of training on brain activity may be facilitated via changes in compensatory modulation of the cerebellar interregional connectivity.