The field of food packaging has been transformed by nanomaterials, which possess distinctive characteristics such as improved barrier qualities, mechanical strength, and antibacterial activity. Nevertheless, some concerns have emerged regarding the possible health hazards linked to their usage, which require a comprehensive toxicological assessment. This chapter offers a thorough examination of the toxicological elements associated with nanoparticles used in food packaging. The chapter provides a detailed discussion of several methods used to evaluate the toxicity of nanomaterials, which include in vitro research, in vivo studies, and computer modelling. The study investigates many factors that affect the toxicity of nanomaterials, including their size, shape, surface chemistry, dosage, exposure length, agglomeration/aggregation behaviour, and biological interactions. These factors are analyzed to understand their impact on defining the safety of nanomaterials. In addition, the discussion covers the legislative framework that governs the use of nanomaterials in food packaging, as well as techniques for communicating and mitigating concerns to minimize exposure. This chapter seeks to offer significant insights into the safety evaluation of nanomaterials used in food packaging. It intends to address existing gaps in knowledge and provide guidance for future research to ensure the creation of safe and environmentally friendly packaging solutions enabled by nanotechnology.