Several studies have examined the genetic factors shared between Parkinson’s disease (PD) and schizophrenia (SZ), but the biological themes underlying their clinical relationship remain less explored. We employed systematic transcriptomic and network analyses (Figure 1) to examine the genes targeted by two sets of antipsychotic drugs (APDs), first-generation APDs inducing Parkinsonism and second-generation APDs typically effective against psychotic symptoms in PD. We also examined two sets of PD drugs, i.e., those that were contraindicated in SZ, or not. We found that, although global brain expression patterns did not effectively differentiate between the targets of two sets of APDs with varying abilities to induce Parkinsonism, they differentiated the targets of two sets of PD drugs, one with contraindications in SZ, and the other without. However, both APD and PD target sets showed differences in mean expression levels in specific brain regions. Moreover, they showed significant enrichment for genes highly expressed in distinct adult and prenatal brain structures, relative to the overall distribution of such genes among all brain-expressed genes. Specific neurotransmitter systems, either individually or in combination, seemed to underlie these drug categories, indicating their differential roles in inducing (or not inducing) symptoms of PD and SZ. Additionally, these target sets formed distinct network modules, representing different biological mechanisms, and exhibited differential proximity to PD- and SZ-associated genes in the human interactome. In summary, our study identified specific spatial and functional features that distinguish the target sets of PD and SZ drugs with different clinical outcomes.