This review aims to explore the toxicological aspects of mercury-based herbo-metallic preparations like cinnabar and "Rasasindura" that are primarily composed of mercuric sulfide (HgS). Cinnabar-containing preparations have been used extensively in Indian and Chinese systems of medicine for treatment of chronic ailments like syphilis, high fever, pneumonia, insomnia, nervous disorders, deafness, and paralysis of the tongue. Contrary to Western medicine, which does not promote the use of mercury due to its toxic effects, Indian and Chinese traditional practitioners believe that mercury-based formulations have potent therapeutic efficacy, while there is no toxicity due to the unique and repeated purification processes employed during preparation. However, lack of proper pharmacovigilance and widespread self-medication has resulted in undesirable effects to certain sections of the consumers of these preparations, which have contributed to the negative publicity for these forms of medicine. Variations in the quality of the preparations coupled with the lack of understanding of the differences in the recommended dosages and treatment strategies adopted by traditional medicine practitioners, further fuels concerns in the Western world on the safety and efficacy of traditional medicine. But in spite of these concerns, concerted efforts to understand the biological interactions and transformations of these preparations are yet to gain momentum. Although scattered reports on the toxicity of these preparations are available in literature, their mechanism of action has not been conclusively established. Long-term pharmacotherapeutic and in-depth toxicity studies are needed to address the apprehensions raised by these herbo-metallic preparations. This review highlights the lacunae in the studies conducted thus far, and assesses the need for further studies to provide significant data to establish the safety and efficacy of such preparations, as well as develop gold standards for stringent quality control of these preparations.