Nanocellulose, particularly bacterial cellulose (BC), has gained increasing attention for its diverse applications in several fields, notability in the food industry. Despite its long history of safe human consumption in Asian countries as “nata de coco”, with no reported adverse health effects, its nanoscalar dimension raises regulatory concerns regarding its safety upon oral ingestion. Consequently, global regulatory bodies, such as the European Commission (through the European Food Safety Authority—EFSA) and the FDA (U.S. Food and Drug Administration), have implemented pre-market safety assessment frameworks to evaluate the potential toxicity of nanomaterials like BC in food applications. This chapter presents a comprehensive overview of the toxicological profile and regulatory landscape of BC, with a focus on its safety for human consumption. The chapter also addresses the existing challenges in the characterizing of BC using conventional nanomaterial assessment techniques, as recommended by EFSA, which are inadequate for its unique structure and highlights the importance of further research to bridge knowledge gaps. Briefly, although the existing studies suggest that nanocellulose, in particular BC, generally exhibits low toxicity and may even confer prebiotic benefits, critical knowledge gaps persist. Further, there is a limited understanding of the long-term fate of nanocellulose in the gastrointestinal tract (GIT), particularly concerning degradation, absorption, and systemic distribution. While current regulatory frameworks emphasize the need for robust risk assessment strategies, challenges remain in adapting these methodologies to structured biopolymers like BC. The chapter concludes with recommendations for future research directions aimed at addressing uncertainties in nanocellulose toxicology and ensuring safe and sustainable integration into food systems.