Herbal drugs, also known as phytochemicals or botanical medicines, are a cornerstone of traditional healthcare, with the World Health Organization (WHO) noting their reliance by approximately 80% of the global population. Despite their historical and widespread use, the assumption of their inherent safety due to natural origins is misleading. The significance of toxicological profiling and standardization to ensure the safe use of herbal medicines. Challenges such as species substitution and adulteration highlight the urgent need for regulatory oversight and stringent quality control. Various bioactive compounds in herbs can pose severe health risks, necessitating comprehensive toxicity evaluations using OECD guidelines. Regulatory frameworks across different regions, including the FDA in the United States, EMA in Europe, and the Ministry of AYUSH in India, are pivotal in maintaining the safety and efficacy of these products. Strategies to mitigate herbal drug toxicity include standardization of manufacturing processes, adherence to Good Manufacturing Practices (GMP), robust regulatory compliance, extensive research on toxicity profiles, education of stakeholders, and vigilant monitoring of adverse events. These measures are essential to fostering the responsible use of herbal medicines and safeguarding public health.