Objective: To evaluate the antibacterial activity of Ocimum sanctum (O. sanctum) leaf extract, alone, and in combination with chloramphenicol (C) and trimethoprim (Tm) against Salmonella enterica serovar Typhi (S. typhi). Methods: The antibacterial activity of ethanolic extract of tulsi, a sanctum, leaf (ME: 500 mu g for 23 S. typhi isolates was determined following agar diffusion. The C (30 mu g) and Tm (5,mu g) activity alone and in combination with TLE (250 mu g) was determined by disk diffusion. The zone. diameter of inhibition (71)1) for the agents was recorded, and growth inhibitory indices (GHs) were calculated. Results: The S. typhi isolates (n=23). which were resistant to both C czrA 6 mm) and Tin (71)1 6 turn), had TLE (500 mu g) ZDIs 16-24 null. The ZDIs of C and Tm were increased up to 15-21 nun and 17-23 mm, respectively. when TIE (250 mu g) was added to the C and Tm discs. The GHs ranged 0.789-1.235 and 0.894-1.352, due to combined activity against S. twin, isolates, of C and TIE and Tin and TLE, respectively. Conclusions: The data suggest that TIE, in combination with C and Tin, had synergistic activity for S. typhi isolates, and hence O. sanctum is potential in combating S. typhi drug resistance, as well promising in the development of non-antibiotic drug for S. typhi infection.