BackgroundAt present, the focus and difficulty of schizophrenia (SCZ) treatment is to improve cognitive function and negative symptoms. Jie-du-qing-nao granules(JQG) , a traditional Chinese medicine(TCM) prescription , has a good clinical effectiveness in enhancing the cognition and negative symptoms of patients with SCZ. However, its clear effectiveness and safety have not been adequately supported by clinical studies. The main objective of this study is to explore the efficacy and safety of JQG for first-episode schizophrenics.Methods/designThis trial is a prospective, randomized, single-centered, parallel-controlled clinical study with double-blind design. A total of 96 eligible participants will be randomly assigned to either the study group or the control group in a ratio of 1:1. Participants allocated to the study group will receive JQG and aripiprazole, control group will receive placebo and aripiprazole. The treatment course will last 12 weeks, with follow-up every 4 weeks. Outcome measurements include Positive and Negative Syndrome Scale (PANSS), self face test , MATRICS Consensus Cognitive Battery (MCCB), TNFα, IL-6, IL-1β, BDNF, vital signs, complete blood count, liver and kidney function tests, urinalysis, and electrocardiograph. Adverse reactions will be evaluated using the Treatment Emergent Symptom Scale (TESS).DiscussionThis study will provide evidence for the efficacy and safety of JQG as a complementary approach, which can be initiated following with antipsychotics therapy. Trial registration Chinese Clinical Trial Registry, ID: ChiCTR1900028250 . Registered on December 16, 2019, http://www.chictr.org.cn/edit.aspx?pid=41880&htm=4 .