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Background: Schizophrenia is a chronic persistent disease with high recurrence rate and high disability rate in the field of psychiatry. Sodium nitroprusside is a nitric oxide (NO) donor and considered a promising new compound for the treatment of schizophrenia. New high-quality clinical trials of sodium nitroprusside in the treatment of schizophrenia have been published in recent years. It is necessary to re-conduct the meta-analysis after the inclusion of these new clinical trials. Our study will conduct a systematic review and meta-analysis of the relevant literature in this field, so as to lay an evidence-based medicine foundation for the efficacy of sodium nitroprusside in the treatment of schizophrenia. Methods and analysis: Randomized controlled trials (RCTs) of sodium nitroprusside in the treatment of schizophrenia were searched through English databases (PubMed, Web of Science, Embase, and Cochrane Library) and Chinese databases (China Biology Medicine disc, VIP, WanFang Data, and CNKI). The extracted data will be inputted into Review Manager 5.3 for Meta-analysis. The included literature will be assessed for bias risk according to the bias risk assessment tools in the Cochrane Handbook for Systematic Reviews of Interventions. Funnel plots will be used to assess possible publication bias. Heterogeneity is tested by I2 and χ2 tests, and the existence of heterogeneity is defined as I2 ≥50% and P ≤0.1. If heterogeneity exists, the random-effect model will be used, and sensitivity analysis or subgroup analysis will be performed to further determine the source of heterogeneity. Prospero registration number: CRD42022341681. [ABSTRACT FROM AUTHOR]