Surface-growing antibiotic-resistant pathogenic is emerging as a global health challenge due to its high economic loss in the poultry industry. Their pathogenesis, increasing antimicrobial resistance, and biofilm formation make them challenging to treat with traditional therapy. The identification of antimicrobial herbal ingredients may provide valuable solutions to solve this problem. Therefore, our aim is to evaluate the potency of nano garlic as the  alternative of choice against multidrug-resistant (MDR) isolates using disc diffusion and microdilution assays. Then, checkerboard titration in trays was applied, and FIC was measured to identify the type of interaction between the two antimicrobials. A disc diffusion assay revealed that neomycin was the drug of choice. The range of nano garlic MIC was 12.5-25 μg/ml, while the neomycin MIC range was 32-64 μg/ml. The FIC index established a synergistic association between the two tested drugs in 85% of isolates. An experimental model was used including nano garlic and neomycin alone and in combination against infection. The combination therapy significantly improved body productivity and inhibited biofilm formation by more than 50% down regulating the , and operons, which are responsible for curli fimbriae production and biofilm formation in serotypes.