Aims: Urinary tract infection (UTI) is a common infection caused by many virulent bacteria. Multidrug resistance (MDR) by bacteria represents a major therapeutic challenge worldwide. MRD bacteria have different mechanisms to avoid antibiotics; one of them is horizontal gene transfer. Such genes, encoding antimicrobial resistance, are easily transferred from one bacterium to another. Magnesium and calcium chloride (MgCl2 and CaCl2) have an effect on the permeability of bacterial cell membrane. We aimed these chemical materials could increase the antibiotics efficiency on multidrug resistance bacteria. 250 UTI specimens were collected to isolate multidrug resistant bacteria. Depending on antibiotics resistance, we selected three species of virulent bacteria: Escherichia coli, Staphylococcus aureus and Proteus mirabilis. Then, we tested the effect of MgCl2 and CaCl2 on their antibiotics resistance. Methodology and results: The results showed that percentage of E. coli in UTI infection is the highest (45%), while Enterococcus faecalis is the lowest (3%). The effect of MgCl2 and CaCl2 on bacterial antibiotics resistance has been tested using different types of antibiotics. The findings showed that MgCl2 has significant effect to aid antibiotics against bacteria. In particular, nalidixic acid has shown more efficiency against E. coli and S. aureus but not P. mirabilis. Using different concentrations of CaCl2 increased the efficiency of gentamycin, amoxicillin and trimethoprim against S. aureus, while has increased the efficiency of ampicillin and nalidixic acid against E. coli. However, CaCl2 has no effect on the efficiency of antibiotics against P. mirabilis. In addition, MgCl2, and CaCl2 had no toxic effects in both T24 and 5637 urinary bladder cell lines. Finally, plasmids were isolated from these species to detect any antimicrobial resistance gene such as qnr-A. Conclusion, significance and impact of study: MDR distribution in the worldwide was increased, we highly recommend the avoidance of the random antibiotic usages. The salts CaCl2 and/or MgCl2 can be used at specific concentration to enhance the antibiotics permeability and therefore to decrease the antibiotic resistance.