Aims: To evaluate the anti-leptospiral activity of Canarium odontophyllum leaves against Leptospira interrogans serovar Bataviae and Leptospira borgpetersenii serovar Javanica. Methodology and results: The extracts (hexane, acetone, methanol and aqueous) used in this study were tested at concentration ranging from 0.049 mg/mL to 25 mg/mL using broth microdilution method. Percentage inhibition (%) was obtained through OD reading at 400 nm. Only methanol extract was incubated with Leptospira to observe population changes under dark field microscope prior to subjected for DNA damaging studies through gel electrophoresis of genomic DNA. Methanol extract showed the highest percentage inhibition of 66% against L.interrogans serovar Bataviae and 74% against L. borgpetersenii serovar Javanica. The IC50 value of methanol extract was 4.60 mg/mL and 2.25 mg/mL against serovar Bataviae and serovar Javanica, respectively. Both Leptospira culture which was treated with IC50 value of methanol extract showed drastic decrease in population compared to untreated Leptospira for both serovar. There was no DNA damage towards serovar Bataviae. However, serovar Javanica exhibited DNA damage as observed from the presence of DNA fragmentation on the gel electrophoresis. Conclusion, significance and impact of study These findings confirmed that methanol leaves extract from of Canarium odontophyllum has a potential to control leptospirosis.