Introduction: Infectious diarrhea (ID) is a highly prevalent disease worldwide that poses a substantial risk to human well-being. In China, numerous clinical studies have investigated the efficacy of Gegen Qinlian decoction (GGQLD) in treating ID. However, there is a need for additional rigorous and evidence-based medical research to enhance physicians’ confidence in their prescribing practices. Methods: Seven Chinese and English databases were systematically searched. The Cochrane Risk of Bias tool was used to assess the quality of the included studies. Meta-analysis was conducted using RevMan 5.3, and Stata 16.0 was used for the sensitivity analysis. Trial sequential analysis was performed using TSA v0.9, and GRADEprofiler was utilized to evaluate the quality of evidence. Results: A total of 12 randomized controlled trials (RCTs) involving 1,240 patients were included. The meta-analysis demonstrated that the combination of GGQLD with conventional Western medicine had better effects on clinical efficacy (relative risk [RR] = 1.15, 95% confidence interval [CI] [1.10, 1.20]), duration of diarrhea symptoms (weighted mean difference [WMD] = −10.96, 95% CI [−11.97, −9.96]), duration of abdominal pain symptoms (WMD = −12.01, 95% CI [−14.12, −9.90]), duration of fever symptoms (WMD = −11.91, 95% CI [−13.39, −10.43]), interleukin-6 levels (WMD = −113.59, 95% CI [−113.03, −108.14]), and tumor necrosis factor-α levels (WMD = −62.18, 95% CI [−65.25, −59.11]) and that no significant adverse reactions occurred (RR = 0.45, 95% CI [0.10, 1.97]). The sample size of the included studies reached the expected size. The quality of evidence for outcome indicators was rated as low or very low. Conclusions: The combination of GGQLD with conventional Western medicine demonstrates promising efficacy and safety in treating ID. Nonetheless, more high-quality RCTs are required to confirm this conclusion.

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