Abstract: Objective To investigate the efficacy of olanzapine and ziprasidone in the treatment of schizophrenia and their effects on glucose and lipid metabolism. Methods Ninety patients with schizophrenia admitted in our hospital from March 2014 to January 2017 were divided into group A and group B according to the random number table method, 45 patients in each group. Group A was treated with ziprasidone, and Group B was treated with olanzapine. The efficacy, glucose and lipid metabolism were compared between the two groups at 6 weeks after treatment. Results There was no difference in PANSS and CGI-S scores between the two groups before and 2, 4, and 6 weeks after treatment(all P>0.05). The scores of positive symptoms, negative symptoms, general spirit and PANSS of group A and group B treated for 4 and 6 weeks were lower than those before treatment(all P<0.05). The effective rate of treatment in group A was 97.78%, higher than 82.22% in group B(P<0.05). After 6 weeks of treatment, the FBS decreased, and INS, LDL, HDL, CHOL, TG increased in group A; the FBS, INS, LDL, CHOL and TG increased in group B; the FBS, INS, and LDL levels in group B were higher than those in group A; the differences were statistically significant(all P<0.05). Conclusion There was no significant difference between ziprasidone and olanzapine in treatment of schizophrenia, but the effect of ziprasidone on glucose and lipid metabolism is relatively small.