Interest in searching and developing new antimicrobial agents to combat microbial resistance has been growing recently. Therefore, a greater attention has been paid to both screening and evaluation methods of antibiotics activity. The present study aimed to evaluate the potency of some antibiotics containing pharmaceutical products of some Egyptian market companies using microbiological assay based on agar diffusion method and using standard strains in order to determine their therapeutic efficacy. These antibiotics such as gentamicin, ciprofloxacin, doxycycline, amoxicillin and ceftriaxone were purchased from local pharmacies and evaluated in the current study. The results of this study showed the relative potency of gentamicin was 41.4%-120% and 28%-41% for ciprofloxacin. While for doxycycline relative potency was 26%-72.6% and 16%-88% for Amoxicillin. As well as ceftriaxone potency was ranged between 48%-97.4%. One product of ceftriaxone, two products from gentamicin and two from amoxicillin were estimated to be within the acceptable range of bioequivalence (80%-120%), while the other products showed unacceptable relative potency. A complaint reporting system about quality and effectiveness problems needs to be considered as a priority source of such information to inform decision-makers. The steadily increasing in bacterial resistance to existing antimicrobial drugs is a significant issue, hence it is imperative to look out new approaches of bacterial therapy Sometimes the effective inhibitory action is not produced when antibiotics are used alone. To overcome this problem, a combination of drugs often used. One approach to treat infectious diseases is the use of combination of antibiotics together or with plant extracts or phytochemicals. For patients with serious infections caused by pathogens resistant to drugs, combination therapy is beneficial and useful. Seven antibiotics were obtained from local pharmacy (gentamicin, ceftazidime, ciprofloxacin, doxycycline, amoxycillin, ceftriaxone, and azithromycin). Minimum inhibitory concentrations (MIC) were determined by broth micro-dilution method, different antimicrobial combinations were studied on 20 Multidrug resistant (MDR) clinical isolates (10 S. aureus and 10 P. aeruginosa). Also, the antibacterial activity of some volatile oils (limonene, rosemary, salvia, thymus, and black pepper), plant extracts (moringa seed, curcumin, and capsicum) and phytochemicals (thymol, and chitosan) were detected against S. aureus and P. aeruginosa isolates using broth micro-dilution method. According to our findings, ceftriaxone and ciprofloxacin or gentamicin together exhibited a substantial synergistic effect against S. aureus. Also, the combination of amoxicillin with ceftazidime was synergistic to reduce MIC by five to six times. Regarding MDR clinical isolates of P. aeruginosa, combination of azithromycin with doxycycline exhibited decrease of MIC of azithromycin by about five to six folds. The combination of gentamicin with ceftriaxone was significant. For natural compounds, thymol, rosemary oil, curcumin, capsicum and moringa seed extract exhibited the highest synergistic activity with the tested antibiotics against S. aureus and P. aeruginosa. In conclusion, the lack of new antibiotics necessitates the improvement of existing ones. Our study shows that antibiotics combinations and antibiotic-natural plants combinations are very promising strategy for combating the complex bacterial resistance.