Abstract Background The pathophysiological mechanisms of schizophrenia are complex and not fully elucidated. This study aimed to investigate changes to total glutathione (T-GSH), glutathione disulfide (GSSG), reduced glutathione (GSH), and the GSH/GSSG ratio before and after electroconvulsive therapy (ECT) for patients with acute relapse of schizophrenia and associations with clinical symptoms. Methods The study cohort included 110 patients with acute relapse of schizophrenia and 55 healthy controls. All patients received 8–10 sessions of ECT. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Results As compared to the healthy controls, schizophrenia patients had decreased baseline GSSG levels (t = -2.115, p = 0.036) and elevated GSH/GSSG ratios (t = 2.141, p = 0.034). Baseline GSSG levels were negatively correlated with both PANSS total scores (beta = -0.369, t = -4.108, p