Objective: Fabrication and analyses of mucoadhesive patches made from chitosan oligosaccharide for the purpose of oromucosal drug delivery. Significance: The mucosal epithelium in the oral cavity, consisting of buccal and sublingual epithelium, has gained significant attention in the last decade as an alternative anatomical site for systemic drug delivery that could potentially minimize the challenges of solid oral dosage and parenteral delivery. In this study, we have fabricated and tested drug-loaded chitosan oligosaccharide-based patches for the oromucosal drug delivery. Methods: The chitosan oligosaccharide (with and without alginate) based patches were fabricated using the conventional solvent casting method and were analyzed for their swelling capacity, hydrophilicity, anti-cancer activity, in vitro drug release, and in vivo drug release activity. The in-house developed artificial saliva was used for the swelling study. Results: Alginate-containing patches showed lesser swelling ability compared to the bare chitosan oligosaccharide-based patches. The former was also found to be more hydrophobic compared to the latter one. Both the unloaded patches restricted the growth of epithelial cancer cells indicating their anti-cancer behavior. In vitro drug release indicated a super case II release pattern while in vivo study demonstrated the release of drug from the patch into the plasma indicating the purpose of the fabricated patch. Conclusions: The chitosan oligosaccharide-based mucoadhesive hydrogel patch fabricated in this study can be highly suitable for possible translational purposes. © 2022 Informa UK Limited, trading as Taylor & Francis Group.