Abdominal aortic aneurysm (AAA) is a segmental, progressive, and fatal vascular disorder, and the current strategy for small AAAs is close observation alone.The purpose of this study is to summarize the available evidence to assess the effects of antibiotics on small abdominal aortic aneurysms (AAA).We searched PubMed, EMBASE, Web of Science, and Scopus from inception to September 29, 2023, and included randomized controlled trials (RCTs) that evaluated the effects of antibiotics on small AAAs in humans. We first performed a meta-analysis to assess the effects of antibiotics on small AAAs. Afterward, network pharmacology analysis was applied to investigate the optimal drug generated from the meta-analysis results. We searched Pharmmapper and GeneCards to obtain the common potential targets of the selected drug and AAA-related targets. The protein-protein interaction network and functional enrichment analysis were performed by the STRING database, Cytoscape 3.7.2 software, and R, respectively. Docking studies were carried out for validation.We incorporated data from six RCTs involving a total of 997 patients. The results of this meta-analysis revealed that roxithromycin exhibited a modest yet statistically significant protective effect in terms of slowing down the AAA expansion rate. Furthermore, our subsequent bioinformatics analysis pinpointed MMP-2, MMP-9, ALB, MMP-3, and CCL-5 as potential therapeutic targets that could be explored for the treatment of AAA using roxithromycin.In conclusion, the study indicates roxithromycin is a promising drug for treating small AAAs and supports its underlying clinical use in small AAAs.Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.