Abstract This paper aims at presenting an overview of the historic and current features concerning the relationship among original peoples, psychoactive drugs, and various forms of anti-drug practices in Latin America. The current expansion of extractivist capitalism in Latin America overlaps with Indigenous peoples' traditional lands, provoking new forms of violence and confrontation. The War on Drugs is being used as a justification to militarize these lands and to criminalize Indigenous populations. Thus, neo-extractivist initiatives in Latin America provoke renewed clashes between Indigenous peoples' interests and local and global elites' purposes. We seek to raise awareness about the relationship between the drug war and Indigenous people's human rights violations as an alert and an invitation for social scientists to engage in theoretical and empirical research on this issue.