Buccal foams containing omeprazole (OME) have been developed as potential drug delivery systems for individuals encountering swallowing difficulties, particularly pediatric and geriatric patients. The buccal foams were formulated from lyophilized aqueous gels of maltodextrin, used as a sweetener, combined with various polymers (alginate, chitosan, gelatin, tragacanth) to fine tune their structural, mechanical, and physicochemical properties. Consistent with the requirements for efficient drug delivery across buccal epithelium, the foam comprised of hydroxypropyl methylcellulose and alginate (HPMC-Alg-OME), exhibited moderate hardness and high mucoadhesion resulting to prolonged residence and increased transport of the active across porcine epithelium. The HPMC-Alg-OME foam induced a 30-fold increase in the drug's apparent permeability across porcine buccal tissue, compared to the drug suspension. The developed buccal foams exhibited excellent stability, as evidenced by the unchanged omeprazole content even after six months of storage under ambient conditions (20 °C and 45% RH). Results indicate that buccal foams of omeprazole may address the stability and ease of administration issues related to oral administration of the drug, particularly for children and elderly patients who have difficulty swallowing solid dosage forms.