The present study was conducted to evaluate the efficacy of some antibiotics and methanol extracts of both Punica granaturm (pomegranate) peel and Cymbopogon citrates (lemon grass) against Escherichia coli and Salmonella Enteritidis (SE) and comparing between them in vitro using sensitivity test and minimum inhibitory concentration (MIC) and in vivo model with regarding to their interactions in broiler chickens, evaluating the antioxidant activities of pomegranate and its effect on poultry meat quality. According to the sensitivity tests, levofloxacin (Levo) and pomegranate peel extract (PPE) were found to have the most effective antibacterial effect against SE. The minimum bactericidal concentration (MBC) of PPE was 46.8 mg/ml and MIC ranged from 1.4 to 23.4 mg/ml. One hundred and twenty, one day old broiler chicks, were divided into 8 equal groups: G1:negative control group without infection, G2: positive control group orally challenged with SE (3x 108 ) CFU/ml at the 10th day of age, G3: infected group treated with levo (10 mg/kg) and PPE (125 mg/ml), G4: infected group treated with levo (10 mg/kg) and PPE (250 mg/ ml), G5: prophylactic group treated with PPE (500 mg/ ml) before infection, G6: infected group treated with levo (10 mg/kg), G7: infected group treated with PPE (125 mg/ ml) and G8: infected group treated with PPE (250 mg/ ml) via crop gavage. Blood and meat quality tests were performed after treatment and at the end of the study at 42 days. Biochemical parameters were carried out included detection of endogenous antioxidants (Malondialdehyde-Thiobarbituric Acid (MDATBA) and superoxide dismutase (SOD)), total serum protein, albumin, globulin and albumin/ globulin ratio. Quality tests included the organolyptic examination, PH, total volatile nitrogen (TVN), tissue TBA and microbiological tests. The obtained data showed that both doses of PPE exert similar bactericidal activity as the standard antibiotic (levofloxacin) with antioxidant effect and significantly (P<0.05) improved both blood parameters and meat quality. Both groups G3 and G5 still have infection. The biochemical analysis revealed that no significant change was recorded among groups in total serum protein, albumin, globulin or A/G ratio after treatment or at the end of the experiment. After treatment, G4 showed a remarkable reduction in blood MDA levels when compared with normal or infected control groups. Regarding to SOD levels after treatment G2 and G5 showed a remarkable decrease while G3, G4, G6, G7 and G8 showed a significant increase. There was no significant difference was recorded at the end of the experiment between the tested groups. The overall results of this study suggested beneficial use of PPE as natural alternative therapeutic agent to synthetic antibiotics for treatment of S. Enteritidis infection in broilers' but not as a prophylactic. PPE give us a great chance in combating microbes and improving meat quality and safely either bacteriologically or chemically.