The lawless jungle, where migrants face treacherous terrain and violent gangs in the hope of a better life, has become a key target for Panama's new President Jose Raul Mulino, who has vowed to shut the route.
"Rivers that were a natural oasis" are now "waters contaminated by feces, even by corpses," Environment Minister Juan Carlos Navarro told AFP.
"We have to bring order to these areas, end this trafficking (of migrants) as soon as possible and ... restore it to its natural state," he added.
"We are currently in the first stages of planning it. I would like to be able to do it as soon as possible," he said of his plan to clean up the jungle on the border between Colombia and Panama.
The project, according to Navarro, includes cleaning and environmental restoration of damaged areas, as well as "economic support" for local communities.
According to the minister, the clean-up would be financed with $3 million provided by the United States.
Washington this month pledged $6 million in funding for migrant repatriations from the Central American nation in the hope of reducing irregular crossings at its own southern border.
Navarro did not specify if the funds for the clean-up would come from that deal.
In 2023, more than 520,000 migrants passed through the perilous jungle.
So far this year, 200,000 people have made the journey, mostly Venezuelans, according to Panamanian authorities.
On Wednesday, Panama border police reported 10 migrants had drowned in a flooded river near the border with Colombia.
Before taking office on July 1, Mulino said there was "huge contamination" in the Darien due to "tons, tons and more tons of garbage."
Navarro denounced the "environmental injustice committed against the Indigenous and native populations of Darien ... where these migrants dump all the garbage in the world."