This study aimed to perform a qualitative synthesis of the available in vitro evidence on the microleakage of commercially available conventional glass ionomer cements (GICs), resin-modified glass ionomer cements (RMGICs), and modified glass ionomer cements with nano-fillers, zirconia, or bioactive glasses. A systematic review was conducted according to the PRISMA 2020 (Preferred Reporting Items for Systematic Review and Meta-Analysis) statement standards. The literature search was performed in Medline (via PubMed), Embase, Web of Science, and Scopus to identify relevant articles. Laboratory studies that evaluated microleakage of GICs, RMGICs, and modified glass ionomer cements with nano-fillers, zirconia, or bioactive glasses were eligible for inclusion. The QUIN risk of bias tool for the assessment of in vitro studies conducted in dentistry was used. After the study selection process, which included duplicate removal, title and abstract screening, and full-text assessment, 15 studies were included. A qualitative synthesis of the evidence is presented, including author data, year of publication, glass ionomer materials used, sample characteristics, microleakage technique and values, and main outcome measures for primary and permanent teeth. Although no statistically significant differences were found in numerous studies, most results showed that RMGICs exhibited less leakage than conventional GICs. All studies agreed that leakage was significantly higher at dentin margins. It was also higher at the gingival margin than at the occlusal margin. Nano-filled RMGICs Ketac N100, Equia Forte, and Zirconomer appear to have less microleakage than conventional GICs and RMGICs. Further investigations using a standardized procedure are needed to confirm the results.