Aims: To investigate the anti-microbial activity of lactic acid bacterial isolates from locally fermented Kunun-zaki beverage. Study Design:  The study was designed to study the anti-microbial effect of lactic acid bacterial isolates obtained from Kunun-zaki beverage. Place and Duration of Study: Department of Applied Microbiology Enugu State University of Science and Technology, Agbani, June 2009 and January 2010. Methodology: Fresh Kunun drink was prepared from millet following standard modified procedures. Isolation of lactic acid bacteria from the beverage sample was carried out using MRS agar medium. Morphological and biochemical characterizations were performed to identify the organisms. Finally, the bacterial isolates were tested for antibacterial activity against clinical pathogens – Bacillus anthracis, Clostridium perfringens, Escherichia coli, Streptococcus faecalis, Micrococcus luteus, Klebsiella pneumonia, Pseudomonas aeruginosa, Bacillus cereus, Bacillus subtilis and Staphylococcus aureus obtained from Microbiology Department Nnamdi Azikiwe University Awka Nigeria. Results: Morphological and biochemical characteristics revealed the presence of Gram’s positive bacteria which were identified as Lactobacillus casei and Lactobacillus brevis. The antimicrobial activity of the isolates (L. casei and L. brevis) against various pathogenic strains recorded 90±0.002% inhibition. Only Micrococcus luteus was absolutely resistant to antimicrobial treatments with Lactobacillus casei and Lactobacillus brevis.  Conclusion: The study concluded that Lactobacillus brevis and Lactobacillus casei from kunun-zaki drink possess strong antimicrobial activity against a wide range of clinical pathogens. Since lactic acid bacteria are known to possess many health benefits, some of the therapeutic effects reported from the consumption of the beverage may be attributed to these organisms.