To investigate if ginkgo biloba extract (Egb-761) can improve tardive dyskinesia (TD) symptoms through increasing the activity of plasma MnSOD. Methods We enrolled a total of 384 schizophrenia patients including 157 TD patients and 227 non-TD patients, as well as 280 normal subjects. The difference of MnSOD level in plasma among these groups were compared. TD patients were then randomly divided into two groups. The treatment group (n=77) and the placebo group (n=75) were treated with 240 mg of Egb-761 or placebo per day for 12 weeks, respectively. The abnormal involuntary movement scale (AIMS) and the positive and negative symptoms scale (PANSS) were used to evaluate the severity of the symptoms in baseline, the sixth week and the twelfth week after treatment. The level of MnSOD activity in plasma was also detected before and after the treatment. Results The level of MnSOD activity was lower in schizophrenia groups than in healthy control group (P＜0.01). In addition, the level of MnSOD activity was significantly lower in TD group than in non-TD group (P＜0.05). Repeated measures analysis of variance showed that group effect (F=4.00, P=0.05), time effect (F=32.17, P＜0.01) and interactive effect of group and time (F=39.04, P＜0.01) were significant in AIMS total score. The AIMS total score of treatment group was significantly lower than that of placebo group at 6-week and 12-week time points (all P＜0.01). Repeated measures analysis of variance showed that time effect (F=23.04, P＜0.01) and interactive effect of group and time (F=6.41, P＜0.05) were significant in the level of MnSOD activity. In addition, the level of MnSOD at baseline was significantly correlated with the reduction of AIMS total score during the treatment period (r=0.27, P=0.018). Conclusion Treatment of Egb-761 can improve symptoms of TD and activity of MnSOD.