The neurophysiological mechanisms of impaired manual dexterity in Parkinson’s disease (PD) have not been elucidated. Hence, our study aimed to compare healthy subjects (HCO) and mildly affected PD patients and to evaluate associations between parameters: (i) striatal dopaminergic function; (ii) activity of the motor cortex; (iii) brain-derived neurotrophic factor (BDNF) and (iv) manual dexterity.The study involved fifteen HCO subjects and thirty patients with mild PD. All subjects were assessed by: (i) Positron Emission Computed Tomography with estimation of striatal [18F]Fluorodopa uptake ratio ([18F]FDOPA PET/CT) to evaluate dopaminergic degeneration; (ii) EEG recorded during bimanual anti-phase index finger movement from which we calculated event-related desynchronization of the beta band; (iii) blood measure of BDNF level; and (iv) the Purdue Pegboard Test (PPT) to evaluate one-hand and bimanual dexterity. PD patients, compared to HCO subjects, exhibited significantly lower: [18F]FDOPA PET/CT uptake ratios in the putamen as well as in the caudate nucleus, values of the beta band ERD, BDNF blood level, and worse manual dexterity. Path analysis based on structural equation modeling indicated significant direct paths from putaminal dopaminergic dysfunction to motor cortex activation and to worsened one-hand manual dexterity. Moreover, the direct path from BDNF level to caudate dopaminergic dysfunction and then caudate dopaminergic dysfunction to bimanual dexterity was significant.Our findings demonstrated that in PD, impaired one–hand manual dexterity was associated with putaminal dopaminergic dysfunction and impaired cortical beta oscillations. Furthermore, the declined bimanual dexterity was attributed to dopaminergic deficiency in the caudate nucleus and decreased BDNF level.