Aim: The aim of the study is to evaluate the bioactive compounds, toxicity and anti-bacterial activities of leaf extract of Vernonia amygdalina. Methodology: The phytochemical analysis of Vernonia amygdalina to detect the presence of bioactive compounds (oxalate, tannins, saponins, flavonoid, cardiac glycoside, alkaloids, steroid, balsams, essential oil and saponin glycoside) was performed using standard methods. The antibacterial activity of the leaf extracts was determined using agar well diffusion method against clinical isolates of Salmonella typhi and Salmonella paratyphi. The toxicity testing was carried out with albino rats using standard method. Results: Different secondary metabolites were found to be present in the leaf extracts after the phytochemical screening. They include tannins, saponins, flavonoids, cardiac glycosides, alkaloids, glycosides, steroid, saponin glycoside, volatile oil and Balsams. Highest zone of inhibition of 10.0 mm and 20.0 mm was recorded against S. typhi and S. paratyphi aqueous and ethanolic extracts of the leaves respectively. Minimum Inhibitory Concentration (MIC) of 100 mg/ml of the aqueous extract was recorded against S. typhi and S. paratyphi. A MIC of 25 mg/ml of the ethanolic extract was recorded against S. typhi and S. paratyphi. The acute toxicity tests reveal no occurrence of death after 2 weeks of administering 5000 mg/kg body weight of the extracts to the albino rats. Conclusion: The results revealed promising potentials of the leaves of V. amygdalina in the treatment of infectious diseases, due to its low toxicity. However, further studies need to be conducted to isolate and characterize the active metabolites present in the leaves.