Aim: Behçet’s disease (BD) is a chronic, inflammatory disease effecting multiple organs. Vascular involvement is a major cause of morbidity and mortality in BD patients. Though clinically well-defined, there is limited information related to disease pathogenesis and vascular incidences in this patient group. The aim of the current study is to investigate the unique metabolic signatures of BD patients with vascular involvement (VBD). Methods: Metabolomic profiling was performed on serum samples of 48 BD patients (18 with vascular involvement) and 40 healthy controls using gas chromatography-mass spectrometry (GC-MS) based untargeted metabolomics analysis. Multivariate and univariate statistical analyses were performed to find altered metabolites and pathways. Results: Untargeted metabolomics results showed that a total of 168 metabolites were identified. The comparison between the groups of BD, vascular involvement in BD and the healthy control group showed that altered amino acid and oxidative stress pathways, especially with glutathione synthesis could be an important stage for developing BD. Conclusion: In the present work, the untargeted metabolomics approach provided new molecular insights for a better understanding of BD pathogenesis and also developing vascular involvement in BD at the metabolite level. The results showed that vascular involvement in BD could be highly linked with amino acid metabolism and also the antioxidant system and these disease-related pathways could be evaluated with further experiments for diagnosis and prognosis of BD and also for vascular involvement in BD.