Parkinson’s disease (PD) is characterized by the selective loss of dopaminergic neurons in the Substantia Nigra and Lewy body formation, resulting in a progressive neurodegenerative disorder with movement defects. The impairment of dopaminergic innervation in PD hinders the two main projection systems from the dorsal striatum (Putamen, Pu, and Caudate Nucleus, CN) from effectively responding to cortical and thalamic signals.A potential role of Oligodendrocytes (OLs) in PD was pointed out by recent works describing GWAS PD variants associated with OLs (Bryois et al, Nat Genet, 2020), PD genes enrichment in OLs (Agarwal et al, Nat Commun, 2020), and reduced OPALIN-positive OLs in PD midbrains (Smajic et al, Brain, 2022).Here, we analyzed single-nuclei transcriptomes from postmortem dorsal striatum sections. We first characterized the diversity of OLs lineage in Pu and CN, profiling new populations with unique transcriptomic patterns. We determined the relevance of specific cell types/states associated with PD, studying both compositional and transcriptomic levels. Remarkably, we found main critical alterations within Pu, specifically in OLs metabolism, and immunological and myelination pathways. These findings correlated with the histological characterization we also performed for a subset of patients, revealing a higher impact of the disease in the Pu region, with an increased number of Lewy Bodies and decreased MBP expression. Finally, we validated OLs populations using spatial transcriptomics with the Xenium in situ platform, confirming OLs lineage heterogeneity. These results demonstrate OLs display PD-related molecular changes, suggesting an impact on myelination and involvement of the immunological system.