Purpose <p>Meningioma is one of the most common primary tumors in the central nervous system (CNS). However, potential systemic therapies for the treatment of meningioma are limited. This study aimed to identify novel therapeutic targets for the treatment of meningioma.</p> Methods <p>In this study, we characterized the differentially expressed metabolites between normal meninges and meningioma tumor tissues with liquid chromatography‒mass spectrometry (LC‒MS/MS). Primary meningioma cells were isolated from patient-derived meningioma tumor tissues. The tumor-promoting roles of γ-aminobutyric acid (GABA) were assessed in vivo and in vitro.</p> Results <p>In this study, 37 amino acids were quantitatively detected, with GABA exhibiting more pronounced differences. Colony formation assay and flow cytometry analyses revealed that treatment with GABA inhibited the proliferation of meningioma cells. Western blot and EGFR fluorescence experiments revealed that GABA inhibited EGFR expression with a notable decrease in BCL-2 expression and a significant increase in BAX expression in the experimental group compared with the control group. The immunohistochemical results showed a significant decrease in the expression of EGFR in the experimental group. And The tumor volume and tumor weight were significantly decreased following treatment with GABA.</p> Conclusions <p>GABA treatment promoted meningioma cell apoptosis which might correlate with the EGFR-BCL-2/BAX signaling pathway. Our study suggested that GABA could be therapeutically useful for managing meningioma.</p>