Cell division protein, FtsZ, has been identified as a new potential antimicrobial target against multidrug-resistant (MDR) and methicillin-resistant Staphylococcus aureus (MRSA). By using computer-aided simulation, the phenolic compounds magnolol and honokiol from Magnolia officinalis were shown to have high anchor energies to FtsZ of S. aureus. The calculated binding energies of magnolol and honokiol for this FtsZ (PDB Code: 4DXD) were established to be -7.6 kcal/mol and -8.2 kcal/mol, respectively. Both of them showed polymerization inhibition efficacy for this FtsZ at 100 ppm, which confirmed the simulation results. Their antibacterial activity against S. aureus including multidrug-resistant (MDR) and methicillin-resistant S. aureus (MRSA) with minimum inhibitory concentration (MIC) values in the range of 8-16 ppm. These findings support the use of computer-aided simulation to screen natural compounds for this cell division protein, FtsZ, and this method can be a quick and promising approach for the development of antimicrobial agents against multi-drug resistant S. aureus.