Objective: Even when endodontic procedures are performed with the utmost care, reinfection can occur. One possible explanation is that contaminated gutta-percha cones were used in the root canals. The study's goal is to assess the antimicrobial activity and efficacy of Neem, Turmeric, and Calotropis Procera in disinfecting gutta percha cones prior to obturation. Materials and Methods: 80 Gutta percha (GP) cones were contaminated with 0.5ml Ferlands standard Enterococcus Faecalis for 10 minutes.20 cones each were treated up to 5 minutes in their prepared neem, turmeric, calotropis and sodium hypochlorite solutions. Then, they placed in BHI broth and vertex is done for 1 minute. One loopful of broth was stroked on 20 blood agar plates of 5 each neem, turmeric, calotropis and sodium hypochlorite. The plates were then incubated for 24 hours aerobically at 37°C and the colony forming units were counted with a digital colony counter. Results: Mean colony forming units were compared in all the groups and there was a statistically significant difference present among the groups (p<0.01). Sodium Hypochlorite (NaOCL)as control group showed average of 5 colony forming units(CFU). Turmeric had the least average of 55 CFU and was the most effective of the experimental groups. Neem and Calotropis had the higher average of 130 CFU and 200 CFU respectively, making it the least effective of the solutions tested. Conclusion : All of the herbal solutions tested positive for disinfection of GP points. When compared to Neem and Calotropis, Turmeric was the most effective and has superior antibacterial activity.