Introduction: Periodontitis is a chronic inflammation that occurs in the periodontal tissue, which damages the sup- porting teeth. Moreover, periodontitis can worsen the metabolic control of diabetes. At the same time, the prolifer- ation activity of fibroblasts in diabetic patients decreases, the activity of collagenase and MMP-9 increases, and the healing time is prolonged. This study aim to test the potential of bioactive compounds of papaya seed through virtual screening in inhibiting MMP-9 activity. Methods: Samples were prepared for bioactive compounds consisting of sal- icylic acid, ferulic acid, resveratrol, vanillic acid, mandelic acid, caffeic acid, methoxyphenylacetic acid. Prediction of drug-like molecules in papaya seeds bioactive compounds was carried out according to the Lipinski Rule of Five. Furthermore, the simulation of the binding of the papaya seed bioactive compound with the target protein was car- ried out using the blind docking method. Then, the interactions formed from the molecular docking simulation are continued with chemical bond interaction analysis and molecular visualization. Results: All compounds contained in papaya seeds can act as drug-like molecules because they meet more than two Lipinski rules. These compounds are predicted to reach intracellular target proteins by crossing cell membranes and triggering specific activities when forming molecular complexes with target proteins. Conclusion: Papaya seed bioactive compounds that were deter- mined through in silico study have potential to inhibit MMP-9 activity in diabetic periodontitis by binding to the active site with weak bond interactions such as hydrogen, Van der Waals, pi, and alkyl.