Canarium odontophyllum is one of the underutilized fruits among the local community in Sarawak, Malaysia. The leaf extracts from C. odontophyllum (6.25 mg/ml to 50 mg/m) were screened against two Gram-positive bacteria (Staphylococcus aureus and Bacillus cereus) and two Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Extraction of the C. odontophyllum leaves using methanol produced the highest yield (5.46%) followed by water (4.0%) and acetone (2.83%) whereas hexane extracted the lowest yield (0.98%). Out of the four bacterial species tested, only S. aureus was found to be susceptible towards the C. odontophyllum leaves extract. Screening result using agar well diffusion method showed that the antimicrobial activity of the acetone and methanol extracts from C. odontophyllum leaves was concentration-dependent towards the growth inhibition of S. aureus. The MIC values for both MeOH and acetone extracts were 0.391 mg/ml. The MBC value of MeOH extract was twice its MIC value whereas the MBC and MIC values of acetone extract against S. aureus were the same. Phytochemical analysis showed that acetone, MeOH and water extracts contain flavonoid, tannin, terpenoid and phenol. These findings conclude that the leaves of C. odontophyllum may contain therapeutically-useful compounds against S. aureus, which are mostly concentrated in the acetone extract. As such, C. odontophyllum have the potential to be developed as an alternative treatment against Staphylococcus aureus-associated skin and soft tissue infections.