Lifestyle factors like lifetime physical activity (LPA) may support motor reserve in Parkinson’s disease (PD), hence the capability to compensate for the effect of dopamine transporter (DaT) loss on motor function. In 20 de novo PD patients, we investigated the potential protective role of LPA on motor function and associated network connectivity by means of resting-state functional magnetic resonance imaging (rs-fMRI). In this group, putaminal DaT integrity was assessed by standardized uptake value ratio (SUVR) for the putamen derived from DaT SPECT imaging. Motor symptom severity was measured using the MDS-UPDRS-III excluding tremor items. General motor performance was quantified by a composite z-score from various motor tests. LPA was assessed using the Historical Leisure Activities Questionnaire and metabolic equivalents were assigned as intensity scores for each reported activity. To examine the potential protective effect of LPA, two moderation analyses were run to investigate the impact of LPA on the relationship between 1) DaT integrity and motor symptom severity (corrected for age), and 2) motor symptom severity and general motor performance (corrected for age and putaminal SUVR). Furthermore, network-based correlation analyses with LPA as covariate of interest were performed using rs-fMRI data (corrected for age and putaminal SUVR, FWE p< .05). A tendency towards better motor performance with higher LPA levels was observed, but moderation analyses were not significant. Nonetheless, greater LPA was positively associated with increased activation in sensorimotor, fronto-parietal and dorsal attention networks. Therefore, LPA may assert protective effects through compensatory network mechanisms, yet further research is needed.