The plants Cissus quadrangularis was collected from kolli hills, Namakkal DT, Tamilnadu. The plant stems were collected and it was dried for room temperature (37 oC) for 10-15 days. The dried stems were grinded as course powder then the powder was filled in soxhlet apparatus. Crude extracts were prepared from that powder using different solvents like Petroleum ether, isopropyl alcohol, ethyl acetate and ethanol. The antimicrobial activities of the extracts were tested against four microorganisms. The antimicrobial activities of Cissus quadrangularis stem extracts were assessed by the presence or absence of inhibition zones and zone diameter values. The Kirby – Bauer method is used for the antimicrobial activity of Cissus quadrangularis stem extracts. Among the four crude extracts of Cissus quadrangularis, the Petroleum ether and Ethyl acetate showed good antimicrobial activity against all the tested microorganisms, Ethanol showed moderate inhibition activity, and Isopropyl alcohol showed least antimicrobial activity against all organisms.