Aim: This study aimed to evaluate and compare the antimicrobial efficacy of root canal sealers of different bases when mixed with herbal extracts. Materials and methods: An evaluation of three sealers (Endomethasone, AH plus, Apexit plus) mixed with three herbal extracts [Emblica officinalis (Amla), Myristica fragrans (Nutmeg) and Salvadora persica (Miswak)] was done against nine strains of bacteria at various time intervals using the agar diffusion test. Moreover, measurement of the mean zones of inhibition was done. Results: The largest zones of bacterial growth inhibition were observed with Endomethasone mixed with Myristica fragrans (Nutmeg) followed in the descending order by AH plus mixed with Salvadora persica (Miswak) and Apexit plus mixed with Salvadora persica (Miswak) respectively. The differences between zones of inhibition among different groups were found to be statistically significant. Conclusion: Zinc-oxide-eugenol-based sealer (Endomethasone) mixed with herbal extracts produced the largest inhibitory zones followed in the descending order by resin-based sealer (AH plus) and calcium-hydroxide-based sealer (Apexit plus), respectively. Clinical significance: Herbal plants such as [Emblica officinalis (Amla), Myristica fragrans (Nutmeg) and Salvadora persica (Miswak)] are rich sources of bioactive compounds that possess antimicrobial properties. Mixing their extracts with endodontic sealers can produce additive antimicrobial effect against microbes found in inflamed pulp.