<p>Human exposure to environmental microplastics and nanoplastics via oral ingestion is a topic of public health and food safety concern. In this Review, the physicochemical properties of drug-delivery nanoparticles were considered to evaluate the biological plausibility of environmental nanoplastics overcoming biological-selective barriers. Physicochemical characteristics probably have a key role in the interaction of nanoplastics with the mucus layer and the intestinal mucosal epithelium. Substantial gaps in experimental designs and analytical methodologies pose a major challenge to fully understanding nanoplastic uptake and should be prioritized for future research.</p>