X-linked dystonia-parkinsonism (XDP) is a recessive neurodegenerative disease endemic to Panay, Philippines. The XDP striatum is notably reported to undergo significant atrophy, neuronal loss, and astrogliosis. However, detailed neuropathological studies characterising the human XDP striatum are limited.To advance our understanding of the human XDP striatum, immunohistochemistry coupled with automated analysis was conducted on post-mortem striatal tissue from 12 XDP and 5 age-matched neurologically normal cases to detail (1) the neurochemical architecture and (2) neuronal and glial populations of the striatal sub-compartments.Neuroanatomical delineation of the XDP striatal compartments, through enkephalin, DARPP-32, and GABAA receptor β2/3 immunolabelling, revealed ‘patches’ of enhanced immunoreactivity, likely to be preserved striosomes rather than preserved matrix. Furthermore, calbindin expression, normally localised to the matrix, appeared upregulated within the XDP striosomes. Together, these observations suggest pathological restructuring of the XDP striatal sub-compartments. Additionally, the XDP striatum presented with selective neuronal vulnerability, indicated by >50% loss of calbindin+ medium spiny neurons and ChAT+ interneurons. Morphometric analysis of remaining XDP ChAT+ interneurons revealed a reduction in somal size and process number. Furthermore, the presence of astrocytosis and microgliosis was identified within the caudate nucleus of the XDP striatum.This study is part of an ongoing investigation to elucidate the neurochemical and phenotypical dysfunction of the human XDP striatum. Subsequent studies will investigate key striatal outputs and other basal ganglia nuclei to further understand XDP neuropathology and identify potential future therapeutic targets.