INTRODUCTION: Carbapenem-resistant Enterobacteriaceae (CRE) infections are associated with increased mortality and higher healthcare costs in hospitalized patients, making it reasonable to explore the effectiveness of strategies for decolonization of intestinal carriage. OBJECTIVE: To evaluate the effectiveness and safety of oral and/or intravenous antibiotics in adults colonized by CRE. METHODS: We conducted a systematic review of randomized clinical trials and nonrandomized studies comparing oral and/or intravenous antibiotic therapy versus no treatment or placebo in adults colonized by CRE. Outcomes assessed included eradication, infection rate, mortality, length of hospital stay, and adverse events. Searches were performed in the Embase, MEDLINE (PubMed), and Cochrane Library. Quality assessment was conducted using the ROB1 or ROBINS-I tool. Meta-analysis was performed using a random effects model in Review Manager, and the certainty of evidence was evaluated using the GRADE methodology. RESULTS: Seven studies comprising 728 participants were included. Decolonization therapy was significantly associated with intestinal carriage eradication (OR: 2.66; 95% CI: 1.55-4.55; I: 0%). There was a trend toward a reduced infection rate (OR: 0.66; 95% CI: 0.26-1.65; I: 4%). Data on mortality and adverse events were limited and insufficient to draw conclusions about differences between groups. The certainty of evidence ranged from moderate to very low. CONCLUSION: This study suggests that decolonization therapy may be effective in eradicating CRE intestinal carriage state, but current evidence is insufficient to determine its impact on infection rates, mortality, or adverse events. Larger, high-quality randomized clinical trials are necessary to generate robust evidence supporting its clinical use.