The antibacterial and antifungal activity of Lantibiotic Nisin and Essential oil Carvacrol against pathogenic and spoilage-forming microorganisms was investigated in this study. The antimicrobial activities of these compounds were observed in vitro on one Gram-positive (Listeria monocytogenes), two Gram-negative (Cronobacter sakazakii and S. Typhimurium) bacterial strains, and one fungus (Candida albicans). The study investigated the effect of combined treatments involving UV-C irradiation along with Nisin and carvacrol as antimicrobial agents on microbial growth, both at 4°C refrigerator temperature storage for two weeks, and on artificially inoculated chicken drumsticks with L. monocytogenes and S. Typhimurium. Total Aerobic Mesophilic, Yeast & Mold, and Enterobacter/Coliform populations were examined using plate counting on PCA, PDA, and VRBA media, for L. monocytogenes, and S. Typhimurium. PALCAM, OXFORD, and Bismuth Sulphite Agar, respectively. The results indicate that samples, which were subject to a combination of UV-C irradiation dose and concentration of antimicrobial agents (2 × MIC), showed a significant decrease in pathogen count (p ≤ 0.05) in comparison to the samples that received only a higher quantity of antimicrobial agents (2 × MIC). C. albicans was the most resistant microorganism to all treatments. In vitro experiments on cell growth indicated that the tested compounds exhibited varying toxicity levels on all tested bacterial species. The study found both synergistic and additive effects in UV-C combinations but did not observe any antagonistic effects. These findings present an optimistic outlook for future research into the antimicrobial mechanisms of Nisin and Carvacrol with UV-C against pathogens.