Salmonellosis, antimicrobial drug residues, and multi-drug resistance are major challenges accounting for a huge loss within the poultry investment scheme. In-vivo and in-vitro antibacterial prospect, utilizing the methanol extract of Lagenaria breviflora (LB), was applied as an alternative therapy for salmonellosis in broilers. Minimum Inhibitory Concentration (MIC), and Minimum Bactericidal Concentration (MBC) were determined and showed an improved inhibition performance. The in-vivo assay was performed on 60 broilers in various treatment groups from treatment 1-6 with 10 times repetition. Treatment 1 was uninfected and untreated. Treatment 2-6 were infected with Salmonella species per os. After 6 days of incubation, treatment 3-6 received treatment with LB extract (200mg/kg, 400mg/kg, 800mg/kg) or ciprofloxacin (20mg/kg), respectively, for 5 days. The broilers in treatment 2, in contrast, did not receive any therapy. Fecal samples from Treatment 3-5 were significant (p≤0.05), indicating lower bacterial counts compared to Treatment 2, and Treatment 1. Elevated PCV, and WBC were lower in Treatment 3-5. These latter groups had hemogram values comparable to infected chickens treated with ciprofloxacin and healthy control chickens. Histopathology showed reversed liver inflammation, and an amelioration of degenerated nephrons, in extract-treated broilers, accompanied by a better control of diarrhoea and dehydration. This study, therefore, established the antibacterial potential of L. breviflora against Salmonella species in broilers. Diarrhea and dehydration associated with salmonellosis were also reversed in extract-treated broilers.