Oral mucositis (OM) is a common side effect of cancer treatments characterized by disruption of the oral mucosa integrity, inflammation, and pain. The treatment strategies to prevent and treat OM are still unsatisfactory, leading to the search of new active compounds, particularly from natural sources, such as Actinidia arguta fruits. A. arguta is a perennial vine and its fruit, commonly known as kiwiberry, has been associated with different therapeutic properties and pro-healthy benefits, particularly antioxidant, anti-inflammatory and anticancer effects. These bioactive properties are due to the fruit outstanding content in phenolic compounds, vitamins, and organic acids, which attracted the researcher's attention for potential application in pharmaceutical industry. The aim of this study is to develop buccal films with A. arguta fruit extract as active ingredient to prevent OM symptoms. The films were prepared by solvent casting after placing 50 g of a buccal film mixture prepared with 1% of HPMC K100 LV EP, 2.5% glycerin, and 100 mL of A. arguta extract as solvent. Different films parameters were assessed, namely physical features (weight: 194.8 mg; thickness: 0.37 mm; disintegration time: 15.05 min; moisture content: 10.53%; swelling capacity: 55.95%), mechanical properties (resistance to extension: 10.11 N; percent of elongation: 36.10%; Young's modulus: 0.0034 MPa) and antioxidant/antiradical activities (TPC = 6.46 mg GAE/g film; FRAP = 49.45 μmol FSE/g film; ABTS = 3.74 mg AAE/g film; DPPH = 4.90 mg TE/g film). In vitro cell assays attested the absence of negative effects on HSC-3 and TR146 oral cell lines. Most important, the compounds release profile were assessed through in vitro and ex vivo models coupled to LC/DAD-ESI-MS quantification and the results revealed high permeation of rutin, quercetin-3-O-glucoside and catechin. Overall, these results highlight the significant potential of buccal films with A. arguta fruit extract to prevent OM condition.