Natural excipients are vital in pharmaceutical formulations, providing benefits such as biocompatibility and sustainability. However, its usage is subject to stringent regulatory frameworks that assure safety, efficacy, and compliance. This analysis looks at worldwide regulatory viewpoints, including guidance from the US Food and Drug Administration (FDA), European Medicines Agency (EMA), and Indian Pharmacopoeia, as well as legislation in Japan and China. It covers important components of safety assessment, such as toxicological evaluation, allergy concerns, and generally recognized as safe (GRAS) status. Compliance requirements such as Good Manufacturing Practices (GMP), paperwork, and analytical procedures are discussed, as well as standardization and quality control problems. The review also identifies regulatory problems, such as variability in natural sources and stability issues, and proposes novel solutions. Furthermore, the study examines sustainability and ethical aspects in excipient procurement and supply chains, with a focus on the regulatory implications of environmentally friendly methods. Finally, emergent trends, such as global regulatory harmonization and the use of digital technology for compliance, are investigated to get insight into the changing regulatory landscape.