Background: Although antibiotics are used to treat typhoid fever, there is a need to look for alternative treatment methods because Salmonella typhi (S. typhi) has become aggressively resistant to standard antibiotic treatments. Methods: This experimental study used the carbonated beverage "7UP" as the extraction solvent to examine the anti-Salmonella activity of Gossypium hirsutum leaf extract on Salmonella typhi.Extraction of bioactive components of the plant leaf, in-vitro and in-vivo anti-Salmonella activity of the extract was carried out using essential microbiological tools. Results: In vitro, anti-Salmonella typhi study showed that ciprofloxacin had the highest zone of inhibition 36.71+0.31 and 36.14+0.10mm against typed (ATCC 14028) and clinical isolates, respectively, while the zones of inhibition of the extract at different concentrations against Salmonella typhi were zero, however, the diameter of zone of inhibition (ZOI) of section at 800 mg/ml was 1.42+0.33 and 1.21+0.01mm against clinical and typed isolates respectively. At larger (3500 mg/ml/kg) and lower (10 mg/ml/kg) doses, there was no death in experimental rats during the acute toxicity assessment. After three days of therapy, the extract reduced salmonella fecal shedding from 71.14±0.31 to 6.02±0.17 × 10³ Cfu/g and guaranteed 100% survival against experimental salmonellosis. Different functional groups in the extract, including alkene, anhydride, alcohol, sulfate, nitro compounds, alkanes, and a carboxylic acid, were observed. Conclusions: The use of ‘7UP' as an extraction solvent for medicinal plants in our community for treating diverse medical ailments, especially infectious diseases, is justified. However, it could pose a toxicological effect.