After attending Isidore Newman School in New Orleans, Plotkin was a college dropout working at Harvard University's Museum of Comparative Zoology when he joined an expedition searching for an elusive crocodilian species in 1978 and was galvanized into returning to complete his Bachelors at Harvard University, his Masters in Forestry at Yale University and his PhD at Tufts University, during which he completed a handbook for the Tirio people of Suriname detailing their own medicinal plants—the only other book printed in Tirio language being the Bible. He went on to do research at Harvard under Richard Evans Schultes, who virtually founded the field of ethnobotany. Documenting the use made by Native American tribes of medicinal plants unknown to formal Western science, just at the moment when traditional shamanic wisdom was disappearing from tribal cultures, Plotkin has raised consciousness in the unsentimental appreciation of indigenous wisdom, coming into general public view first with Tales of a Shaman's Apprentice, 1993. The book has been translated into five languages and formed the theme of the IMAX film "Amazon" which was nominated for an Academy Award.
In 1995 Plotkin and prominent Costa Rican conservationist Liliana Madrigal formed the Amazon Conservation Team (www.amazonteam.org) to foster partnerships with indigenous groups to protect their culture by passing traditional learning to a new generation in Suriname, Colombia, and Brazil. Plotkin continues to work with the Tirio of Suriname, and in Brazil as well.
Plotkin received the San Diego Zoo Gold Medal for Conservation (1993) and the Roy Chapman Andrews Distinguished Explorer Award (2004). Time magazine called him an "Environmental Hero for the Planet" (2001) and Smithsonian magazine hailed him as one of "35 Who Made a Difference" (2005), along with other notables like Bill Gates, Steven Spielberg, and fellow New Orleanian Wynton Marsalis.
In March 2008, Plotkin and Madrigal were among those chosen as "Social Entrepreneurs of the Year" by the Skoll Foundation (www.skollfoundation.org).