Bee venom (BV) is a rich source of secondary metabolites from honeybees (Apis mellifera L.). It contains a variety of bioactive ingredients including peptides, proteins, enzymes, and volatile metabolites. This study investigated the antibacterial effects of the bee venom obtained from honey bees (Apis mellifera L.) against bacterial fish pathogens, such as Lactococcus garvieae (Lg1, Lg2, Lg3), Vibrio anguillarum (Va1, Va2, Va3), Yersinia ruckeri (Yr1, Yr2, Yr3), and Aeromonas hydrophila (Ah1, Ah2, Ah3) and the expression levels on the antibiotic resistance genes hly and fbp (hemolysin and fibronectin-binding prot) of them. It was determined that bee venom had an antibacterial effect against L. garvieae, L. anguillarum, and Y. ruckeri strains, while it had no effect only against Ah3 and Ah2 bacterial strains. As staded by the gene expression of hly (hemolysin) and fbp (fibronectin-binding protein), among the antibiotic resistance genes the effect levels of bee venom on bacterial species varied, although it affected antibiotic resistance and gene expression level in all bacteria. It was revealed that the expression level was the highest for V. anguillarum strains, whereas it was below the control group for L. garvieae. i.e the effect of bee venom on the resistance mechanism for L. garvieae was much less compared to V. anguillarum. Based on the results in the current study it could be concluded that applying bee venom to pathogenic bacteria that cause mortality in the aquaculture sector could induce the defense-related gene and change the broad-spectrum biocontrol activity at the molecular level.