Objective: In this paper, a computational study, including molecular docking, was accomplished for ciprofloxacin metabolites and some natural compounds, then a practical study of that compounds alone and in combination was applied against resistant methicillin STAPHYLOCOCCUS AUREUS (MRSA) isolates. Methods: A docking software was used for molecular docking of the enzyme isomerase (3UWZ from protein data bank PDB) with ciprofloxacin (CIP) and its metabolites like sulfo-ciprofloxacin (Sulfo-CIP), oxo-ciprofloxacin, desethylene-ciprofloxacin, acetyl-ciprofloxacin, and natural compounds such as flavonoids (rutin, quercetin, hesperidin), phenols (thymol, gallic acid), phenolic acids (salicylic acid), terpenoids (menthol, eucalyptol) and coumarins (7-hydroxy coumarin). An antibacterial application for the highest binding energy of metabolites and natural compounds alone and in combination by using well diffusion method applied to ten of (MRSA) isolates. Results: Docking results revealed that rutin, CIP, and Sulfo-CIP were the highest binding energy values of-106.76,-104.64, and-102.23 K/cal, respectively. The diameter of the inhibition zone pointed to the antibacterial activity against MRSA isolates, and it showed a range from 16-18, 18-22, and 18-19 mm in order. But the inhibition zone diameter in the combination of rutin with Sulfo-CIP ranged from 28 to 35 mm. Conclusion: Metabolite Sulfo-CIP showed up high antibacterial activity close to CIP theoretically and in vitro; also, the relationship with natural compound rutin showed a synergistic effect.