Objectives <p>To summarize and analyze existing evidence regarding the clinical performance of high-viscosity glass-ionomer-based materials (HVGIs) and bulk-fill resin-based composites (BFs) in patients with occlusal or proximal cavities in permanent teeth.</p> Materials and methods <p>A literature search was conducted using PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Scopus, and Web of Science (WOS) (last update: April 19th, 2024). Randomized control trials (RCTs), retrospective and prospective comparative cohorts were included. Manual searching was performed for twelve relevant dental journals. The primary outcome was the retention of the restoration. The evaluation of included studies, data extraction, and study selection were completed by two independent reviewers. The Cochrane risk-of-bias tool (RoB 2) and the Newcastle-Ottawa scale were used to assess the quality of included studies. A quantitative meta-analysis was conducted, and the overall quality of the evidence was evaluated.</p> Results <p>Five RCTs and one retrospective study were included, of which one had a high risk of bias and the others had an unclear risk of bias. In meta-analyses, HVGIs were associated with a less favorable outcome on retention both at one (<i>p</i> = 0.013) and two-year follow-ups (<i>p</i> &lt; 0.0001) compared with BFs. The quality of the evidence was very low.</p> Conclusions <p>Very low certainty evidence suggested that BFs presented favorable clinical performance on retention and marginal adaptation in Class I and II restorations in permanent teeth comparing HVGIs. Nevertheless, HVGIs with a resin-based coating showed acceptable clinical behavior.</p> Clinical relevance <p>For patients with a high caries risk, HVGIs serve as a direct restorative alternative for the posterior permanent teeth; however, they should be carefully considered as bulk-fill composite resin alternatives for long-term restoration.</p> Registration <p>PROSPERO (CRD42024535999).</p>