Porphyromonas gingivalis (P. gingivalis) is a Gram-negative, anaerobic rod-shaped bacterium that has been implicated as a keystone pathogen in chronic periodontitis. Such disease is characterized by inflammation and affects the individual’s gums, which eventually leads to tissue destruction and tooth loss. There is an increasing number of evidences on the role of P. gingivalis in Alzheimer’s disease pathogenesis. Inhibition of gingipain K, one of the virulence factors of P. gingivalis, has been considered as an effective strategy for treating Alzheimer’s disease, especially for individuals with concomitant chronic periodontitis. The objectives of this project are to evaluate the binding interactions of a set of FDA-approved drugs in the active site of P. gingivalis gingipain K and to determine their inhibitory activity against the gingipain K. Structure-based virtual screening on gingipain K was performed through molecular docking simulation of 300 FDA-approved drugs obtained from the ZINC 15 database. The top ten compounds (fludarabine, phenylephrine, levetiracetam, midodrine, formoterol, lamivudine, olsalazine, benazepril, ketorolac and diltiazem) with relatively high docking scores were selected for subsequent biological screening. Through gingipain K enzymatic assay, the gingipain K activity was determined by measuring the absorbance at 405 nm over 15 minutes. Results from the molecular docking studies showed that the compounds engaged primarily in hydrogen bonding, π-π stacking, salt bridge and pi-cation interaction with the surrounding residues, namely Trp391, Thr442, Ala443, His444, Gly445, Asn475, Cys477, Ser511, Tyr512, Trp513, Asp516 and His575. The presence of functional groups in the ligands, such as carbonyl groups, amino groups, amido groups, hydroxyl groups as well as aromatic rings was considered important for the binding interaction between ligands and gingipain K. Olsalazine (% gingipain K inhibition = 32.43% at 50 μM and IC50 = 93.44 ± 1.89 μM) was identified as the top hit compound among the ten compounds from the biological evaluation. It is considered as a promising compound for further development as a therapeutic agent for the treatment of AD. Keywords: Porphyromonas gingivalis gingipain K, Alzheimer’s disease, drug repositioning, in silico study, biological evaluation