Oral ulcerative lesions are painful and debilitating, particularly for immunosuppressed patients undergoing chemotherapeutic/irradiation treatment. Their clinical management requires multiple drugs to be administered simultaneously. Current formulations available to patients require frequent dosing, leading to poor compliance and suboptimal clinical outcomes. In this study, we prepared wheat germ agglutinin (WGA)-conjugated liposomes (WGA liposomes) to serve as bioadhesive drug carriers that can encapsulate various classes of drugs, rapidly bind to oral epithelial cells within minutes, and stay on the cells to provide sustained, localized drug release for days. Fluorescence binding studies found a significant increase ( < 0.05) in the binding of WGA liposomes to oral cells in as short an incubation time as 1 min compared to that for nonconjugated liposomes. WGA liposomes encapsulating model drug amoxicillin showed sustained in vitro drug release, and the released drugs provided potent antimicrobial activity against in an oral epithelial-bacterial coculture system. Exocytosis studies confirmed that the WGA liposomes stayed within the oral cells for 48 h, after which the cells completely removed the liposomes. Moreover, cell viability studies showed that there was a significant reduction in oral cell damage when the bacterially infected cells were treated with amoxicillin-loaded WGA liposomes compared to the untreated controls. These results point to the great potential of the lectin-conjugated liposomes as cell-binding drug-delivery systems in achieving localized, sustained drug release for the management of oral ulcerative lesions and other related complications.