Medicinal plants contain various bioactive compounds that are significant in both traditional and contemporary therapeutic approaches, addressing a wide array of diseases. In addition to the benefits and historical application of herbal medicines, significant issues regarding safety, toxicity, and regulatory frameworks related to medicinal herbs exist. This chapter assesses the critical factors affecting the safe utilization of medicinal plants, encompassing potential adverse effects, challenges related to standardization and quality control, and regulatory obstacles across different global regions. Alkaloids, glycosides, tannins, and heavy metals are substances that raise toxicological concerns due to their potential to damage vital organs, disrupt cellular functions, or induce cancer when ingested in excessive amounts or over prolonged durations. Additionally, environmental factors, such as soil quality, climate, and toxin exposure significantly influence the toxicity levels of plants. This chapter emphasizes the importance of recent scientific advancements, such as metabolomics, genomics, and analytical chemistry, in developing standardized methods for the identification and quantification of bioactive constituents in medicinal plants. Moreover, studies grounded in evidence regarding the pharmacokinetics, pharmacodynamics, and toxicity of medicinal plants are crucial for the revision and enhancement of regulatory standards. The use of medicinal plants in healthcare systems offers numerous advantages; however, stringent safety and regulatory measures are essential to safeguard patient health. This chapter emphasizes the necessity of a comprehensive strategy that integrates stringent regulatory measures with scientific research to facilitate safe therapeutic applications while safeguarding public health.