Background: Enterococcus faecalis (E faecalis) is a major cause of persistent periradicular lesions in the endodontically treated teeth. In recent literature, natural extracts have received considerable attention as potential antimicrobial agents. Objective: The aim of the current study is to compare the antimicrobial effectiveness of natural extracts namely Propolis, Essential oil of Artemisia pallens, and Black seed oil with that of 2% Chlorhexidine gluconate (CHX Gluconate) against E faecalis. Materials & Methods: This comparative study was conducted on 40 samples (n=10 for each Group I: Propolis, Group II: Essential oil of Artemisia pallens, Group III: Black seed oil, and Group IV: 2% Chlorhexidine Gluconate). The methods briefly involved inoculation of lawn cultures of E faecalis (ATCC-29212) into Mueller Hinton agar plates. The test irrigants were added to the wells made on the agar media, and an Agar Diffusion Test (ADT) was performed for all samples. The comparisons of the bacterial zones of inhibition (ZOI) were done between groups. ANOVA with a post hoc Tukey’s HSD test was used for statistical analysis of obtained data. Results: The ZOI scores of Group I (Propolis), Group II (Essential oil of Artemisia pallens), Group III (Black seed oil) and Group IV – (CHX Gluconate) were 22.5, 32.60, 34.70 and 24.55 respectively. Conclusion: The Black seed oil demonstrated the maximum antimicrobial activity against Enterococcus faecalis and could be used as an alternative to conventional root canal irrigants.