The dynamic drug-resistance characteristics of bacterial strains are excruciating, and various antibiotics have no discernible effect against life-threatening infections. The current study focuses on a strategy to increase the susceptibility of Bacillus cereus, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae against different antibiotics. Polyamines are the essential biogenic compounds found in prokaryotic and eukaryotic organisms. They carry out pivotal roles in the survival, growth, and tissue development of organisms. These small hydrocarbon molecules were found to be positively charged at physiological pH. Several studies have identified the role of polyamines in enhancing the sensitivity of bacteria towards antibiotics. The present study evaluates the desirable use of polyamines and their precursor, ornithine as potential synergistic agents to increase bacterial susceptibility. Putrescine and spermine supplementations showed the best effect on Gram-negative and Gram-positive bacteria, respectively. Results from the present study confirm the enhanced efficacy of antibiotics against bacteria when supplemented with polyamines.