Over the past few decades, extensive research has been carried out on the evaluation of the different plants extracts for antimicrobial activities. The present study is carried out to examine the antibacterial activity of Pedilanthus tithymaloides. It is a medicinal plant, which is found to posses varied medicinal activities including anti-inflammatory, wound healing along with antioxidant property. In the present work, methanol, n-butanol, chloroform, ethereal, ethyl acetate extracts of Pedilanthus tithymaloides were selected. The in vitro antimicrobial activity of these extracts was carried out against various gram positive and gram-negative bacteria. This was carried out with the help of disc plate method. The zone of inhibition formed against these microorganisms was measured for the determination of the antibacterial efficacy of the different plant extracts. Of the selected extracts, n-butanol extracts showed significant antibacterial potential against Bacillus subtilis, Proteus mirabilis, Streptococcus pyogens, Aeromonas, Klebsiella pneumoniae, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. In addition, petroleum ether extracts showed activity against Aeromonas species. The ethyl acetate and chloroform extracts showed antibacterial activity only against Klebsiella pneumonia.