Bacterial biofilm is a major factor in the development of multidrug-resistant phenotypes and the progression of chronic infections, as biofilm forms robust shields around bacterial cells enabling them to escape from antibiotic's destructive effect. One solution is multi-targeting antimicrobial natural products that combat biofilms and re-sensitize resistant bacteria to unworkable antibiotics. Two Egyptian bee propolis samples were collected from different regions and ethanolic extracts were prepared. Anti-staphylococcal and anti-biofilm activities against MDR Staphylococcus aureus revealed that propolis extracts differed in their potency and exhibited average MICs of (362 ± 0.19 and 432 ± 0.063µg/mL) for West-Nile and Upper-Egypt propolis samples respectively. Propolis extracts revealed a potent inhibitory effect on staphylococcal biofilm formation (from 49.5% to 29%) at their MICs. Both propolis extracts eradicated successfully the preformed staphylococcal biofilm within two hours of treatment (from 97.4% to 25). Moreover; the anti-adherence activity of both extracts at different concentrations (1X MIC, 1/4, and 1/8 MIC) was similar (from 63.6% to 56.5%) after two hours of exposure to propolis. The effect of combination with antibiotics was assayed by the Kirby-Bauer test which revealed noticeable synergistic effects that were more obvious in Upper-Egypt propolis extract. Synergistic effects with different classes of antibiotics were expressed as a percentage with; Amikacin (56.3%), Penicillin G (53%), Ampicillin (52%), Clindamycin (39.5%) then Ciprofloxacin (32.5%). Egyptian propolis was proved to be a promising anti-biofilm and antibiotic-saving natural product.