Objective: This systematic review and meta-analysis (SRM) investigated the potential of garlic (Allium sativum) against cariogenic oral microorganisms. Design: The SRM was conducted following PRISMA guidelines and registered in PROSPERO (CRD420251133140). Randomized clinical trials (RCTs) evaluating garlic or garlic-derived compounds on cariogenic oral microorganisms were included. A literature search was performed in the main scientific databases. Meta-analyses were performed using RevMan software, with standardized mean difference (SMD) as the effect measure, and a random-effects model was applied with 95 % confidence intervals. Risk of bias was assessed using the Cochrane tool, and the certainty of evidence was graded according to the GRADE approach. Results: Nine RCTs fulfilled the inclusion criteria, predominantly assessing S. mutans, followed by Lactobacillus spp. and C. albicans. All included trials employed garlic-based mouthwashes as the intervention and consistently demonstrated significant antimicrobial activity. In meta-analysis, compared to chlorhexidine, garlic reduced S. mutans at 1 week (SMD = −0.73, 95 % CI = −1.39 to −0.07, I² = 73 %; p = 0.03), had a slightly lower effect at 2 weeks (SMD = 1.27, 95 % CI = 0.09–2.44, I² = 90 %; p = 0.03), and showed no difference at 1 month (SMD = −0.54, 95 % CI = −2.78–1.70, I² = 96 %; p = 0.64). Compared to sodium fluoride, it demonstrated superior activity at 2 weeks (SMD = −0.79, 95 % CI = −1.22 to −0.36, I² = 0 %; p = 0.0003). Most studies had a low risk of bias, and the certainty of the evidence was rated low. Conclusions: Garlic-based mouthrinses show significant antimicrobial activity against cariogenic microorganisms, supporting their potential as a phytotherapeutic strategy for biofilm control. However, the evidence remains limited, demonstrating the need for further high-quality clinical trials to confirm long-term efficacy.