Introduction: The aim of the study was to compare the antibacterial efficacy of 0.125% chlorhexidine (CHX) and nanocurcumin when used alone and in combination with a 980 nm diode laser against Enterococcus faecalis biofilm. Materials and methods: Forty eight extracted human single rooted teeth were selected. Their crowns were resected at the cementoenamel junction (CEJ), and their roots were mechanically prepared. They were sterilized and then infected with Enterococcus faecalis for three weeks. They were divided randomly into four groups in accordance with the type of irrigant used. Group (A), normal saline. Group (B), 0.125% CHX. Group (C), nanocurcumin irrigant. Group (D), nanocurcumin irrigant and a 980 nm diode laser. The antibacterial efficacy was evaluated before and after irrigation. Results: The reduction percentage was 93.5% in group (B), 90.26% in group (C), 99.5% in group (D), and 0.15% in group (A). Conclusion: The combination of nanocurcumin irrigant and a 980 nm diode laser is a promising modality in elimination of Enterococcus faecalis completely from the root canals.