The present study was aimed to evaluate the in-vitro and in-vivo antibacterial effects of the Typha elephantina aqueous extract (TE.AQ), ethanolic extract (TE.ET) and T. elephantina methanolic extract (TE.ME) against eight selected clinical pathogens. The test samples were tested for in-vitro analysis (by disc diffusion method) at different concentrations of 5, 15, 25, 50 and 100 mg/dL against both gram positive and gram-negative strains. The highest potential was observed in TE.ME at a concentration of 100 mg/dL against Pseudomonas aeruginosa exhibiting 19.67 ± 0.577 mm zone of inhibition (ZOI). The same fraction also showed good activity against Staphylococus aureus with ZOI of 17.50 ± 0.70 mm. The TE.ET was found most active against P. aeruginosa and Streptococcus pyogenes having ZOI of 18.53 ± 0.503 and 16.2 ± 1.55 mm respectively at a concentration of 100 mg/dL. The most sensitive bacteria P. aeruginosa was selected for in-vivo study (using poultry chicks) for induction of infection in chicks. The effects of TE.AQ, TE.ET and TE.ME were determined at concentrations of 300 mg/kg body weight based on hematological parameters, liver enzymes and gross pathological findings of lungs and livers. The findings of the in-vivo study in chick’s model showed that treatment of experimental animals with TE.ME significantly restored the hematological parameters, liver enzymes and architecture of lungs and livers. Based on scientific evidence, the current study suggests that TE.ME may serve as a best and new natural antibacterial agent and can be used against infections caused by P. aeruginosa.