Introduction: Appropriate disinfection of root system is crucial for the success in endodontics. The most common bacterial species detected in root canals in both deciduous and permanent teeth is Enterococcus faecalis. Experimental reports evaluating anti-bacterial effectiveness of natural remedies, such as propolis, are increasing. Objectives: This systematic review was designed to answer a question: "Is propolis extract more effective against Enterococcus faecalis compared with other intra-canal medicaments?". Material and methods: Following inclusion and exclusion criteria, thirteen studies from PubMed, Scopus, and Web of Science databases were included in this systematic review, according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement guidelines. Study protocol was registered in the international prospective register of systematic reviews (PROSPERO), number: CRD42023445364. Results: Based on meta-analysis, bactericidal activity against E. faecalis for propolis extract was significant compared with control samples (saline). Of the selected intra-canal medicaments, chlorhexidine demonstrated the most bactericidal effect against E. faecalis. In contrast, calcium hydroxide was less effective compared with propolis. Conclusions: Propolis extract seems to be more effective against E. faecalis compared with saline and calcium hydroxide. However, further research is necessary to establish its reliability in endodontic clinical scenarios.