The global population is rising at an alarming rate and is projected to reach 10 billion by 2050, necessitating a substantial increase in food production. However, the overuse of chemical pesticides, including antibacterial agents and synthetic fertilizers, poses a major threat to sustainable agriculture. This review examines the ecological and health impacts of antibacterial agents (e.g., streptomycin, oxytetracycline, etc.) in horticultural crops, focusing on their effects on non-target organisms such as beneficial microbes involved in plant growth promotion and resistance development. Certain agents (e.g., triclosan, sulfonamides, and fluoroquinolones) leach into water systems, degrading water quality, while others leave toxic residues in crops, leading to human health risks like dysbiosis and antibiotic resistance. To mitigate these hazards, sustainable alternatives such as integrated plant disease management (IPDM) and biotechnological solutions are essential. Advances in genetic engineering including resistance-conferring genes like EFR1/EFR2 (Arabidopsis), Bs2 (pepper), and Pto (tomato) help combat pathogens such as Ralstonia solanacearum and Xanthomonas campestris. Additionally, CRISPR-Cas9 enables precise genome editing to enhance inherent disease resistance in crops. Emerging strategies like biological control, plant-growth-promoting rhizobacteria (PGPRs), and nanotechnology further reduce dependency on chemical antibacterial agents. This review highlights the urgent need for sustainable disease management to safeguard ecosystem and human health while ensuring food security.