Guyabano plant has become increasingly well-known due to its curative properties. This study determined the efficacy of Annona muricata (Guyabano) leaves as bio-control agent against Staphylococcus aureus. The study employed experimental design with mean and one-way ANOVA as statistical tools. Staphylococcus aureus strains were bought at the Department of Science and Technology while samples of Guyabano leaves were collected at Mandug, Davao City. One hundred grams of leaves were used to take out Guyabano leaf extract using rotary evaporator. Utilizing disk diffusion method with three trials and three replications to determine zone of inhibition, results showed that after 24-hour treatment, there was no zone of inhibition on the experimental variable using 100 percent concentration of Guyabano leaf extract. However, zone of inhibition of oxacillin was active in the zone of 11.5 mm. Vancomycin was very active in the zone of 17.17 mm, while distilled water did not yield any zone of inhibition. Both experimental and control group did not yield any significant difference in its zone of inhibition on Staphylococcus aureus. Results showed that Guyabano leaf extract could not be a bio-control agent for Staphylococcus aureus; hence, cannot be used in treating diseases caused by these bacteria. Further studies are warranted.