Biodegradable polymeric packaging materials are being studied for their potential to replace traditional petroleum-based ones for food contact applications. However, potential safety concerns associated with the utilization of these biodegradable polymers have not been studied in detail. In this study, we conducted non-targeted screening and migration studies on two types of biodegradable milk packaging materials, which were composed of a mixture of polylactic acid (PLA), poly(butylene adipate-co-terephthalate) (PBAT), polybutylene succinate (PBS), and cellulose. In particular, we monitored the transfer of migrating substances from the packaging materials into a food simulant (50% ethanol) and into a real food (fat free and whole milk). A screening study identified seven compounds in the biodegradable packaging bags, including degradation products of antioxidants, lubricants, and plasticizers such as triethylene glycol, diethyl succinate, glycerin, 2,4-di-tert-butylphenol, and 13-docosenamide were identified. The migration studies indicated that the types and amounts of migrating substances transferred into the real food were appreciably lower than those transferred into the food simulant. Most of the detected migrating substances were below the levels established in the European Union regulations. However, the triethylene glycol levels (68-144 mg/kg) in the food simulant exceeded the limits (60 mg/kg) for one of the packaging materials tested. A safety assessment suggested that there is a low level of safety risk associated with one of the biodegradable packaging materials. This study provides important insights into the safety of biodegradable packaging materials that might be used in the food industry.