Objective:To investigate the clinical efficacy and safety of amisulpride in the treatment of schizophrenia.Methods:Ninety patients with schizophrenia admitted to Quzhou Third Hospital from August 2020 to March 2022 were included in this study. They were randomly divided into an observation group and a control group ( n = 45/group). The control group was treated with olanzapine, and the observation group was treated with amisulpride. All patients were treated for 8 consecutive weeks. Total response rate, Positive and Negative Syndrome Scale score, Clinical Global Impression Scale-Severity of Illness score, glucose and lipid metabolism indicators, Treatment Emergent Symptom Scale score, and adverse reactions were compared between the two groups. Results:Total response rate was 88.89% (40/45) in the control group and 93.33% (42/45) in the observation group. There was no significant difference in total response rate between the two groups ( χ2 = 0.14, P > 0.05). After treatment, the PANSS score [(52.14 ± 3.99) points] and CGI-S score [(3.05 ± 0.86) points] in the observation group were significantly lower than (56.38 ± 4.05) points and (4.34 ± 0.92) points in the control group ( t = 5.00, 6.87, both P < 0.001). The levels of fasting plasma glucose [(5.25 ± 0.33) mmol/L], total cholesterol [(4.08 ± 0.67) mmol/L], triglyceride [(1.29 ± 0.35) mmol/L], and low density lipoprotein-cholesterol [(2.60 ± 0.31) mmol/L] in the observation group were significantly lower compared with the control group [(6.02 ± 0.51) mmol/L, (4.71 ± 0.59) mmol/L, (1.61 ± 0.26) mmol/L, (2.91 ± 0.34) mmol/L, t = 8.50, 3.61, 4.92, 4.52, all P < 0.001]. High density lipoprotein-cholesterol level in the observation group was significantly higher than that in the control group [(1.57 ± 0.36) mmol/L vs. (1.18 ± 0.42) mmol/L t = -4.73, P < 0.001]. Treatment Emergent Symptom Scale score in the observation group was significantly lower than that in the control group [(2.39 ± 0.58) points vs. (2.87 ± 0.62) points, t = 3.79, P < 0.05]. The incidences of drowsiness [6.67% (3/45)], constipation [8.89% (4/45)], and weight gain [2.22% (1/45)] in the observation group were significantly lower than those in the control group [73.33% (33/45), 28.89% (13/45), 17.78% (8/45), χ2 = 4.14, 4.64, 4.44, P < 0.05]. Conclusion:The efficacy of sulfapride in the treatment of schizophrenia is equivalent to that of olanzapine. Sulfapride is better than olanzapine in improving symptoms and reducing disease severity and has better safety.