Study’s Novelty/Excerpt This study investigates the antibacterial activity of Vernonia amygdalina (bitter leaves) extracts against clinical isolates of Salmonella, addressing the urgent need for new antibacterial agents due to rising drug resistance. The research highlights the phytochemical composition of V. amygdalina, including alkaloids and saponins, and demonstrates significant inhibitory effects at specific concentrations, with a notable 11 mm zone of inhibition for the ethanolic extract. The findings suggest that V. amygdalina could be a promising candidate for developing new anti-Salmonella treatments, contributing to the management of salmonellosis in underdeveloped nations. Full Abstract Salmonellosis is becoming a common illness in underdeveloped nations, and specifically, typhoid fever is a major public health concern due to its high likelihood of recurrence. Salmonella has become resistant to numerous drugs, making it necessary to look for effective novel antibacterial substances from alternative sources, including plants. The antibacterial activity of Vernonia amygdalina (bitter leaves) extracts was assessed in this study against ten (10) Salmonella species clinical isolates. The bitter leave was cleaned, dried, and ground into powder. The phytochemical content of the leaves was extracted using ethanol and aqueous solvent; the extracts' antibacterial activity was tested against clinical isolates of Salmonella. Alkaloids, cardiac glycosides, saponins, steroids, tannins, and glycosides were among the constituents present, according to the phytochemical analysis. The highest zone of inhibition was 11 mm for the ethanolic extract at 100mg/mL concentration demonstrated against SS 4 isolate, while 9 mm was the highest zone of inhibition for the aqueous extract at 100mg/mL concentration against SS 6 isolate. For both extracts, the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of all Salmonella isolates tested were found at 50 mg/mL and 100 mg/mL concentrations, respectively. V. amygdalina has antibacterial activity against Salmonella and should be investigated further for potential application in developing anti-Salmonella medications and managing salmonellosis.