Trametes species are polyporoid white rot fungi that are important in medicine as well as serving as bioremediator and biodegrader of cellulosic waste. The present study investigates the bioactive compounds and antistaphylococcal properties of extracts obtained from raw and fermented Trametes polyzona. T. polyzona was collected from dead woods in farmland around Akungba-Akoko (7 o 27' 32.4''N 5 o 45' 07.8''E) and subjected to submerged and solid-state fermentation. The raw and fermented samples were extracted using acetone and methanol. The mycochemical and antistaphylococcal properties of the extract obtained from raw and fermented T. polyzona were assessed using standard methods. Extract obtained from T. polyzona subjected to submerged fermentation exhibited higher and better antistaphylococcal activity (28.00 mm) on Staphylococcus aureus isolated from blood when compared to other extracts. The minimum inhibitory concentration of the extracts against Staphylococcus aureus ranged from 100mg/mL to 400mg/mL. Gas chromatography Mass Spectrophometric (GC-MS) analysis of the sample confirmed the presence of fourteen bioactive compounds of fatty acid group. Results from this study revealed that extracts obtained from T. polyzona contain bioactive compounds with potent antistaphylococcal properties that can be exploited by biopharmaceutical companies.