Resumen: Biopolymers are increasingly explored as safer and more sustainable food packaging materials. This study evaluated the migration behavior of intentionally and non-intentionally added substances (IAS and NIAS), as well as the safety of gelatin and xanthan gum blends reinforced with microcrystalline cellulose, with and without oxygen plasma treatment, incorporating glycerol and limonene as plasticizers. Migration tests were conducted according to European Union (EU) Regulation No. 10/2011 using simulants of different polarities, and IAS/NIAS were analyzed by gas chromatography–mass spectrometry and ultra-high-pressure liquid chromatography–quadrupole time-of-flight mass spectrometry (GC–MS and UPLC-QTOF-MS). Films containing limonene were also evaluated for antioxidant activity. Results showed that plasticizer migration is strongly influenced by simulant polarity, glycerol predominantly migrated into hydrophilic media, whereas limonene and its derivatives exhibited higher migration in fatty simulants. Ethanol 95% acted as a conservative worst-case simulant, promoting extensive migration, while substantially lower migration levels were observed in isooctane and tenax plasma treatment resulted in modest changes in volatile compound migration, while significantly enhancing the antioxidant activity of limonene-containing films. Although overall migration levels were low under most of the tested conditions, NIAS formation, particularly from limonene degradation, highlights the need to account for chemical stability and simulant type when assessing bio-based films. Overall, the study demonstrates that film composition, surface modification, and simulant characteristics jointly influence migration behavior and functional performance under the evaluated conditions reinforcing the need to adapt current regulatory frameworks to the specific behavior of biopolymeric packaging materials. Idioma: Inglés DOI: 10.3390/foods15050867 Año: 2026 Publicado en: Foods 15, 5 (2026), 867 ISSN: 2304-8158 Financiación: info:eu-repo/grantAgreement/ES/DGA/T53-23R Tipo y forma: Artículo (Versión definitiva)