Aim:To compare and evaluate the antimicrobial efficacy of neem, ginger, neem plus ginger and 5.25% sodium hypochlorite and to determine its effectiveness in decontaminating "gutta percha cones" Materials and Methods:A concentrated extract of neem, ginger and neem plus ginger are used to check for the antimicrobial efficacy using the agar well diffusion method. Presence of zones of diffusion were identified against 3 common gutta-percha contaminants namely E.coli, E.faecalis and Staph aureus. New gutta-percha cones, freshly taken out of the packet using sterile tweezers were then decontaminated for 1minute using 6%neem, 6%ginger and 6% neem plus ginger and 5.25% sodium hypochlorite separately. Then, it was placed in a nutrient broth to check for the presence of turbidity. Results:The zones of inhibition were formed around both neem and ginger natural extract, in which neem plus ginger group showed almost equivalent antimicrobial efficacy in comparison to 5.25% Sodium hypochlorite. The broth remained clear even after 24 hours of incubation. Conclusion:We observed in this study that neem plus ginger extract is indeed effective as a GP decontaminant and it holds a promising future as a medium for storage of GP cones.