Sex differences are evident in nearly all complex traits and disease. Various diseases, including but not limited to, autoimmune, neurological, and psychiatric disorders, display sex differences in prevalence, incidence, onset, progression, or severity. To improve treatment for such diseases, it is crucial to uncover the molecular basis for sex differences and their consequences on organ and systemic function. Parkinson’s disease (PD), a neurodegenerative condition that is prevalent in two and four percent of people over the age of 60 and 80, respectively, displays a strong male bias. Specifically, there is male bias in onset age and disease severity, with prevalence and incidence ~1.5 times higher in males. PD is characterized by the loss of dopaminergic neurons in the substantia nigra region of the brain. Sex differences in gene expression are evident in all tissues, including in the substantia nigra. These sex differences in substantia nigra gene expression may be contributing to the observed phenotypic sex differences in PD. Sexually differentiated traits and phenotypes stem from a combination of factors, including genetics (gene variants-by-sex interactions, XY chromosome complements, genomic imprinting), the hormonal milieu, and gene regulation. Here, we performed a meta-analysis of sex differences in human substantia nigra in PD patients and controls using RNA-sequencing datasets. Novel and established disease pathways that have been identified will be discussed as well as the biological mechanisms (sex chromosome complements and/or gonadal hormones) underlying transcriptomic sex differences in substantia nigra.