Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder that impacts the lives of many individuals worldwide. We conducted a systemic review and meta-analysis of randomized controlled trials (RCTs) to assess both the effectiveness of rifaximin in alleviating IBS symptoms and its potential adverse effects. PubMed, Web of Science, Embase, the Cochrane Library, Scopus, and Google Scholar were searched from inception until August 20, 2023, for studies comparing rifaximin with placebo in the resolution of symptoms among IBS patients. Risk ratios (RRs) and their corresponding 95% confidence intervals (CIs) were derived for all the outcomes of interest. Six RCTs were pooled in this analysis. The results showed improved abdominal distension with rifaximin over the control group. Overall symptom relief at the end of the treatment period and follow-up period was also observed in the patients receiving rifaximin. However, no significant differences were found between the rifaximin group and the control group for the outcomes of abdominal pain, nausea, headache, vomiting, diarrhea, sinusitis, bronchitis, and upper respiratory tract infection. The results of our meta-analysis support the use of rifaximin in the treatment of IBS, owing to its safety and effectiveness. Future RCTs should be conducted to assess this topic of interest more extensively.