Aim: To evaluate and compare the antimicrobial efficacy of 0.5% phytochemical extracts of Andrographis Paniculata (AP), 2% Chlorhexidine (CHX) and 5.25% Sodium hypochlorite (NaOCl) as an endodontic irrigant against Enterococcus faecalis. Methodology: Forty freshly extracted human single rooted mandibular premolars were selected, decoronated and standardized to 12mm root length. Cleaning and shaping was done using ProTaper__ampersandsignreg; (Dentsply) up to size F3 and irrigated with 3% NaOCl. Contamination of the specimens was carried out for 21 days at 37__ampersandsignordm;C. The specimens were then divided into four groups (n=10) for irrigation with 0.5% AP, 2% CHX, 5.25% NaOCl and distilled water as control. Before and after irrigation, microbiological samples were collected using sterilized paper points, and efficacy was expressed as reduction in microbial load using Colony Forming Units. Statistical analysis was performed using One-way Anova/Kruskal-Wallis test with Tukey__ampersandsignrsquo;s Post Hoc test. Result: In the root canals, the 0.5% herbal extract of AP was found to be equally effective to 2% CHX and highly effective than 5.25% NaOCl against Enterococcus faecalis with a marked decrease in the number of CFU at the 48th hr. from 2.6 x10__ampersandsignsup3; to 0.9 x10__ampersandsignsup3;. The values were statistically significant with p__ampersandsignlt;0.5. Conclusion: Being a herbal extract with antimicrobial efficacy similar to 2% CHX, 0.5% AP seems to be a better alternative. However further tests and randomised clinical trials are required on AP to use it as an endodontic irrigant in vivo