This systematic review aimed to evaluate the use of different nanoparticles for their ability to impart antimicrobial properties to conventionally inert gutta-percha when it is coated with nanoparticles. After registering with PROSPERO (CRD42023420939), the search was conducted using the PubMed, Cochrane, Scopus, CINAHL, and Google Scholar with predefined keywords. The research question was constructed on PICO as "Does gutta-percha coated with various nanoparticles provide antibacterial activity against root canal microbes compared to conventional gutta-percha points?". A total of five relevant in-vitro studies published in English were included. Nanoparticles used for coating included nanopropolis, silver-curcumin, chitosan, silver, and zinc oxide. Micro-organisms tested comprised of Enterococcus faecalis, Escherichia coli, Staphylococcus aureus, and Candida albicans. Higher concentration of nanoparticles and prolonged coating duration resulted in increased antimicrobial activity, irrespective of the type of nanoparticle, as compared to conventional gutta-percha. The highest risk of bias was identified in reporting of blinding, randomisation, sampling techniques, and sample size calculation. Fewer studies, as well as heterogeneity of methodologies and results preclude the recommendation of a specific nanoparticle for coating gutta-percha. Key Words: Antimicrobial efficacy, Endodontics, Gutta-percha, Micro-organisms, Nanoparticles.