Background: Root canal irrigants play an important role in pediatric endodontics due to bizarre internal configurations such as horizontal anastomoses and internal connections. Sodium hypochlorite is the most effective irrigant solution, but its potential toxicity issues necessitate the search for new alternatives. Aim: to compare the antibacterial effectiveness of sodium hypochlorite, 635 nm diode laser, ozonated water, and Nigella sativa as root canal irrigants against Enterococcus faecalis in deciduous teeth. Design: A total of 450 extracted primary anterior teeth were used. For 24 hours, specimens were infected with E. faecalis, then allocated into seven test groups randomly, including 2.5% Sodium hypochlorite (NaOCl), diode laser 635 nm, ozonated water, Nigella sativa oil, diode laser-NaOCl, diode laser-ozonated water, diode laser- Nigella sativa oil, and two control groups. After disinfection, all specimens were agitated with sterile saline solution, and paper points #30 were inserted into the canals to inoculate the bacteria on agar plates. Subsequently, methylene blue was inserted into the canals and activated according to the groups. The histological ground sections for all teeth were done and evaluated under the light microscope. Results: The highest percentage of bacterial reduction was 97.46% for the diode-Nigella sativa group, without a statistically significant difference from other groups. Conclusions: When combined, the 635 nm diode laser and Nigella sativa oil can eliminate E. faecalis from primary root canals.