Objective: To explore the effect of aripiprazole, ziprasidone and olanzapine in the treatment of schizophrenia and influence on glucolipid metabolism, body weight and cognitive function. Methods: 120 patients with schizophrenia who were treated in the hospital from January 2021 to December 2024 were selected as research subjects, and were randomly divided into aripiprazole group, ziprasidone group and olanzapine group by drawing lots, with 40 cases in each group. The symptom improvement status [positive and negative symptom scale (PANSS)], glucolipid metabolism related indexes [fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC)], body weight status and cognitive function [Montreal cognitive assessment scale (MoCA)] were compared among the three groups before treatment and after 3 months of treatment. The adverse reactions during treatment were recorded in the three groups. Results: After 3 months of treatment, the PANSS scores in the three groups were significantly reduced compared with those before treatment (P<0.05), and the olanzapine group had the most significant differences (P<0.05). The results of glucolipid metabolism and body weight showed that TG in aripiprazole group and FPG, TG, TC and body weight in olanzapine group were increased significantly (P<0.05). The MoCA score in the three groups was significantly improved after drug treatment (P<0.05), among which the aripiprazole group and the ziprasidone group improved more. Conclusion: The three drugs have their own advantages and disadvantages in the treatment of schizophrenia and metabolic effects. There are no significant differences in adverse reactions during treatment. It is necessary to use drugs reasonably in combination with clinical practice.