The study included the collection of samples of raw cow milk to isolate Leuconostoc bacteria, samples were sub cultured on De-Man Rogosa Sharpe-Vancomycin medium, the pure colonies were selected and subjected to the cultural and microscopically tests, according to that 25 cocci bacterial isolates were obtained, then isolates were subjected to biochemical tests. Result of tests showed that 12 isolates belong to the genus Leuconostoc out of 25 cocci bacterial isolates, Vitek2 system was used as a supplementary step. Results of final identification showed that 3 sub species were obtained included Leuconostoc mesenteroides ssp. cremoris 9 out of 12 isolates, while it was 2 isolates of Leuconostoc mesenteroides ssp. mesenteroides and one isolate Leuconostoc mesenteroides ssp. dextranicum. The study included the collection of 15 isolate of diarrhea causative bacteria which subjected to cultural and microscopically, biochemical tests and Vitek 2 system, about the results of identification, 9 isolates out of 15 isolates belonged to Escherichia coli,3 isolates of Shigellagroup,2 isolates of Salmonella ser. paratyphi A and one isolate of Vibrio cholerae, the selected isolates were tested to Antibiotic sensitivity test against 11 antibiotics, the results showed that all isolates were resistant to Ampicillin and sensitive to Imipeneme. Screening of L. mesenteroides ssp. cremoris isolates was done to select the more efficient isolate producing bacteriocin by using well diffusion method, the result showed that L. mesenteroides ssp. cremoris (Lc3) and L. mesenteroides ssp. cremoris (Lc4) isolates gave the highest inhibition against E. coli, Shigella group, Salmonella ser. paratyphi A and Vibrio cholerae, the diameters were 13, 12, 12 and 12 mm respectively for the L. mesenteroides ssp. cremoris (Lc3) isolate, while the L. mesenteroides ssp. cremoris (Lc4) isolate diameters were 13, 12, 12 and 11mm respectively. The synergistic effect between bacteriocin of both isolates L. mesenteroides ssp. cremoris (Lc3) and L. mesenteroides ssp. cremoris (Lc4) with antibiotics was studied against multidrug resistant diarrhea causative bacteria. Synergistic effect between bacteriocin of both isolates with antibiotics was observed. The activity of antibiotics with bacteriocin was increased, like Cefixime, Tetracycline, Trimethoprim-sulfamethoxazole, Ampicillin antibiotics against E. coli, and Cefotaxime, Ceftriaxone, Trimethoprim-sulfamethoxazole, Cefixime antibiotics against Shigella group, and Trimethoprim-sulfamethoxazole antibiotic against Salmonella ser. paratyphi A and Ampicillin, Trimethoprim-sulfamethoxazole, Cefixime antibiotics against Vibrio cholerae.