Objective <p>This systematic review evaluated whether incorporating plant-derived extracts into glass ionomer cement (GIC) enhances its antimicrobial properties against cariogenic microorganisms.</p> Methods <p>A comprehensive search of PubMed, Scopus, Web of Science, and Cochrane Library was conducted according to PRISMA guidelines and registered in PROSPERO (CRD420251156866). In vitro and in vivo studies assessing antibacterial activity of plant-extract-modified GICs were included. Risk of bias was evaluated using the JBI checklist for in vitro and Cochrane Risk of Bias 2 (RoB 2) tool for in vivo studies.</p> Results <p>Twenty-seven studies met the inclusion criteria. A wide range of plant extracts including propolis, <i>Salvadora persica</i> (Miswak), Neem, Cinnamon, Thyme, sage, lemongrass, and <i>Acacia nilotica</i>, were incorporated into different GIC formulations. Most studies demonstrated enhanced antibacterial activity of modified GICs compared with conventional controls, particularly against <i>Streptococcus mutans</i>, the primary initiator of dental caries. Propolis, especially in ethanolic form, showed dose-dependent inhibition comparable to chlorhexidine in some studies. Miswak-modified GIC demonstrated sustained suppression of <i>S. mutans</i> and <i>L. acidophilus</i>, while Neem and <i>Acacia nilotica</i> extracts exhibited strong broad-spectrum activity attributed to their high phenolic and flavonoid content. Thyme and Cinnamon extracts similarly improved antimicrobial effects, whereas lemongrass showed selective inhibition of <i>S. mutans</i> only.</p> Conclusion <p>Incorporation of plant extracts into glass ionomer cements enhances their antimicrobial activity, suggesting a promising strategy for improving their ability to inhibit microbial growth. However, standardized methodologies and clinical studies are needed to validate long-term effectiveness and optimize formulations for clinical use.</p>