<p>This study aimed to develop a novel fresh-cut product containing underutilized vegetable leaves (from radish, beet and celery) and combined natural antimicrobials to enhance its microbiological safety. Replacing a traditional leafy vegetable (Creole lettuce) with a horticultural by-product (beet leaves) in the developed fresh-cut product (50% purple Creole lettuce, 25% arugula and 25% beet leaves) resulted in significantly higher antioxidant capacity (FRAP) and total polyphenol content. Moreover, the replacement enhanced sensory attributes such as color (6%), turgor (9%), flavor (2%) and crispness (2%). On the other hand, the study also explored various methods of applying natural antimicrobials in the developed product: by immersion as disinfectants (using chlorine, citric acid, and oregano essential oil -OEO) and as food additives (OEO, nisin, and various combinations). A comprehensive treatment applied natural antimicrobials: citric acid immersion (0.5%, 5&#xa0;min), followed by OEO (600 ppm) and nisin (500 IU/g) addition before bag sealing. This treatment significantly could control native microflora during at least 3 days of refrigerated storage and could reduce the counts of inoculated <i>L. innocua</i> and <i>E. coli</i> by 5 log CFU/g. In conclusion, a novel fresh-cut product with vegetable by-products was successfully developed and the application of combined natural antimicrobials significantly reduced a simulated microbiological contamination.</p> Graphical Abstract <p></p>