Aim: The aim is to test the antimicrobial activity of Andrographis Paniculata, Azadirachta indica (neem), and Curcuma Longa (curcumin) as a root canal irrigant, against Staphylococcus aureus and Candida albicans using agar diffusion test. Sodium hypochlorite (NaOCl) served as a standard control for comparisons. Materials and Methods: The bacterial strains of C. albicans and S. aureus culture were grown overnight (18-20 h) in the brain heart infusion broth at 37°C and inoculated in Mueller-Hinton agar plates. Antibacterial inhibition was assessed using agar well-diffusion method using the methanolic extracts of the three plants to be tested and NaOCl. Bacterial inhibition zone around each well was recorded. The results were tabulated and analyzed statistically for significance. Results: The novel A. paniculata showed significantly higher zone of inhibition against C. albicans (P < 0.0001) compared to the experimental irrigants. Against S. aureus, it exhibited similar results as that shown by NaOCl (P > 0.05). Conclusion: Zones of inhibition exhibited by novel herbal agent A. paniculata were higher against C. albicans and similar against S. aureus, when compared to NaOCl. © 2018 Journal of Conservative Dentistry.