|There is an urgent need for the development of novel affordable plant based natural antibacterial agents in order to combat against the emergence of antibiotic resistance, resulting from the indiscriminate use of currently available antibiotics. Therefore, this study evaluated the in vitro antibacterial activity and minimum inhibitory concentrations (MIC) of aqueous, methanol, acetone and hexane extracts of the leaf Talinum paniculatum against Escherichia coli (ATCC 25922) and Staphylococcus aureus (ATCC 25923). Agar well diffusion method was performed to evaluate antibacterial activity of each leaf extract at concentrations of 100 mg/mL and 50 mg/mL. Additionally, broth dilution technique was used to determine MIC. The results revealed, for the first time, that each crude leaf extract exhibited antibacterial activity against both E. coli and S. aureus. The largest zones of inhibition against E. coli and S. aureus were observed for 100 mg/mL methanolic and aqueous leaf extracts, respectively. It is concluded that antibacterial potential of the leaf T. paniculatum is mediated primarily via its phytoconstituents, such as alkaloids, phenols, saponins, tannins, steroids, triterpenes and flavonoids. These bioactive constituents present in the leaf are able to hinder peptidoglycan synthesis in bacterial cell wall, destroy bacterial membrane structures, alter surface hydrophobicity, change cell signaling pathways and modulate quorum-sensing and therefore, restrict the growth of microorganisms. Consequently, leaf of T. paniculatum is a promising source to develop potent, cheap and natural antibacterial agents.