This in vitro study compared the antibacterial efficacy of triple antibiotic paste (TAP), diclofenac sodium (NSAID), and pantoprazole (PPI) against Enterococcus faecalis. The combination of TAP + PPI produced the largest inhibition zones, followed by diclofenac + PPI, TAP alone, diclofenac alone, and PPI alone. These findings suggest that combining nonantibiotic agents with antibiotics may enhance root canal disinfection and help reduce antibiotic resistance.