Meningiomas are among the most common primary tumors of the central nervous system (CNS) and originate from the arachnoid or meningothelial cells. Risk factors for the disease include exposure to ionizing radiation, head trauma, and family history. Surgery is the first option of treatment for meningioma, but depending on the location and invasion patterns, complete removal of the tumor is not always feasible. Literature shown several specific unfoldings of this disease when comparing male versus female patients; for example, in one hand, its incidence is higher in female patients, on the other hand, male patients usually develop the malignant and more aggressive type. Here, we compare the proteomic profile of tumor biopsies of male and female patients diagnosed with grade I meningioma and list several differentially abundant proteins between the two groups that ultimately reflected in different enriched pathways. For male patients, the enriched pathways were mostly involved in neutrophil degranulation, cell-matrix organization, antigen processing, and the presentation of exogenous peptides; for the female group, pathways related to the organization of cellular components and organelles, and RNA splicing. Tackling on these differences is important to better understand this disease and, ultimately, provide individual treatments.