Background <p>Recurrent aphthous stomatitis (RAS) is an idiopathic inflammatory condition of the oral mucosa, affecting approximately one-fifth of the population. Oxidative stress (OS) has recently been suggested to contribute to the etiopathogenesis of RAS. Thiols are potent antioxidants that play vital roles against oxidation. This study aimed to determine how OS contributes to the pathophysiology of RAS by analyzing the thiol/disulfide parameters.</p> Methods <p>This cross-sectional study was conducted with a total of 67 participants (31 patients with clinically diagnosed RAS and 36 healthy, age- and gender- matched controls) at a university hospital from January 2022 to June 2023. Blood samples were taken from patients during the active ulcer phase. Native thiol, total thiol, and disulfide levels were measured in the serum of patients and controls. The ratios of disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol were calculated. The parameters were compared between the groups.</p> Results <p>No significant differences were found between the patient and control groups regarding the calculated thiol/disulfide homeostasis parameters. A significant negative correlation was observed between age and total thiol (<i>P</i> &lt; .001, <i>r</i> = − .572).</p> Conclusions <p>Although OS is widely believed to play a pivotal role in the pathogenesis of RAS, conflicting findings in the literature suggest that the underlying mechanisms may be more complex and multifaceted. Therefore, more comprehensive studies are needed to clarify the oxidant and antioxidant mechanisms in RAS.</p>