Herbal medicines have been utilized for centuries across diverse cultures and continue to represent a significant component of global healthcare systems, with the World Health Organization estimating that approximately 80% of the population in developing countries relies on traditional herbal remedies for primary healthcare needs. Despite their widespread acceptance and perceived natural safety, herbal medicines are not without risks, as adverse effects, herb-drug interactions, contamination with heavy metals and pesticides, adulteration with synthetic pharmaceuticals, and intrinsic toxicity pose substantial safety concerns. This article aims to provide a comprehensive review of the safety, toxicity, and regulatory aspects governing herbal medicines, with particular emphasis on toxicological evaluation methodologies, quality control measures, and the critical importance of pharmacovigilance systems. Key themes explored include the scientific approaches to preclinical and clinical safety assessment, the pervasive challenges of ensuring product quality in the face of adulteration and environmental contamination, the heterogeneous regulatory frameworks that exist across major regions including the European Union, United States, China, and India, and the obstacles inherent in achieving standardization and evidence-based validation of herbal products. The article further examines post-market surveillance mechanisms and highlights persistent gaps in adverse event reporting systems specific to herbal medicines. Looking forward, the harmonization of international regulatory standards, implementation of digital pharmacovigilance platforms utilizing artificial intelligence and big data analytics, advancement of phytochemical fingerprinting technologies, and integration of herbal medicines into mainstream evidence-based medical practice represent crucial pathways toward optimizing safety profiles and ensuring that traditional knowledge is preserved while meeting contemporary scientific and regulatory expectations.