OBJECTIVE: Substance use disorder (SUD) is a critical public health problem. The use of methamphetamine is increasing daily worldwide. The aetiology of SUD is related to numerous factors that have not been fully elucidated. It is known that there are some changes in oxidative stress in substance use disorder. However, to the best of our knowledge, there is no study showing changes in thiol/disulphide homeostasis (TDH) in methamphetamine use disorder (MUD). METHODS: Forty-four male patients with MUD and forty-five healthy male controls were included in the study. Only patients who had used methamphetamine in the last three months were included. Blood samples were taken from the patients one day after hospitalization and after detoxification for measurement of the thiol/disulphide level. RESULTS: The levels of native thiol, total thiol, and disulphide in the MUD group were significantly higher than in the control group. At the end of the detoxification period, the levels of native thiol and total thiol did not change significantly, but an increase in the disulphide level was observed. CONCLUSION: The results of our study show that there was a shift in the disulphide direction in the TDH, which is an indicator of oxidative stress in the patient group, and this shift continued after the detoxification period of between 5 and 21 days. There is no other study in the literature evaluating TDH in patients with MUD. Therefore, our study is important for clarifying the aetiopathogenesis of SUD.