Trump took a potshot at the French leader in an address on Wednesday in which he recounted how he had coerced France into agreeing to triple its drug prices.
French President Emmanuel Macron said on Thursday that the US was "breaking free from international rules" and "gradually turning away" from some of its allies.
"Multilateral institutions are functioning less and less effectively," Macron said in his annual speech to French ambassadors.
"We are living in a world of great powers with a real temptation to divide up the world," he added.
Macron's comments come after a string of strongly worded statements by the Trump administration, which have sent ripples of concern among many of Washington's staunchest allies.
Chief among them is US President Donald Trump's escalating rhetoric regarding the annexation of Greenland, the world's largest island and a territory of Denmark.
Trump has long floated the idea of purchasing the island which lies mostly in the Arctic circle, citing its strategic location and saying it was vital for US national security.
US Secretary of State Marco Rubio said on Wednesday that he would meet Danish officials next week to discuss the Trump administration's intention to "acquire" Greenland.
Trump doubled down on the idea this week and the White House has refused to rule out using military force to seize the island in the north Atlantic.
The leaders of France, Germany, Italy, Poland, Spain and the UK joined Denmark’s Prime Minister Mette Frederiksen in a statement earlier this week reaffirming that the mineral-rich island, which lies between the two continents, "belongs to its people."
However, Macron said on Tuesday that he did not believe that the US would move to "violate" Denmark's sovereignty.
"I cannot imagine a scenario in which the United States of America would be placed in a position to violate Danish sovereignty," Macron told France 2.
"Greenland is a territory under Danish sovereignty and it will remain so," added Macron, speaking on the sidelines of a summit of Ukraine's allies.
Frederiksen said a US annexation of Greenland would effectively signal the end of NATO.
"If the United States decides to military attack another NATO country, then everything would stop - that includes NATO and therefore post-World War II security," she told TV2 on Monday.
'Donald, you have a deal'
Other recent moves in Washington have caused further concern, including the Trump administration's decision on Wednesday to suspend participation in dozens of UN agencies and other international organisations, stating their work was promoting "woke" initiatives.
The US has also seized Venezuela-linked oil tankers and captured Nicolás Maduro on narco-terrorism charges.
On Wednesday evening, Trump mocked Macron in an address to Republican lawmakers where he recounted how he had coerced France into agreeing to triple its drug prices by threatening to hike tariffs on all French imports to America.
Trump claimed he asked the French leader to raise prescription drug charges because Americans are allegedly paying "14 times" more than French consumers.
Macron reportedly initially refused, prompting Trump to allegedly issue an ultimatum, ordering Macron to either agree to his demands or face a 25% tariff on all French products.
"Donald, you have a deal. I would like to increase my prescription drug prices by 200% or whatever. Whatever you want, Donald, please don't tell the population, I beg you," Trump said, imitating Macron.
Neither Macron nor the French government have responded to Trump's remarks.