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Introduction: Plants have been used for health disorders and to prevent diseases including epidemics since times immemorial. The knowledge of their healing properties has been transmitted over the centuries within and among human communities. Aims and Objectives: To evaluate and compare the antimicrobial potential of herbal extracts, namely neem (Azadirachta indica), tulsi (Ocimum sanctum), bitter gourd (Momordia charantia), and arka (Calotropis procera) as endodontic irrigants against Enterococcus faecalis and Candida albicans in vitro. Materials and Methods: Agar well diffusion test was performed. The inoculums of E. faecalis and C. albicans were streaked on the blood agar plate, and wells were made using cork borers. The prepared herbal extracts of the test samples were loaded onto agar plate. The plates were incubated at 37°C for 24 h. The inhibition zones indicating the antimicrobial potential were measured using a millimeter scale and results were analyzed statistically. Results: Bitter gourd showed the maximum zones of inhibition followed by neem, tulsi, and calotropis for both E. faecalis and C. albicans. Conclusion: The tested irrigants showed significant antimicrobial efficacy against E. faecalis and C. albicans. Thus, the use of herbal alternatives as root canal irrigants might prove advantageous considering the undesirable characteristics of presently used irrigants.