Gaddafi, known for his controversial statements, did not say who might want to kill Obama but gave the examples of the assassinations of Presidents John F. Kennedy and Abraham Lincoln, as well as black rights leader Martin Luther King.
"I fear that they could liquidate this young man or force him to submit to their imperialist policies," Gaddafi told a university gathering of his supporters in Sirte, without specifying who might put Obama under pressure.
"Obama is a flicker of hope in the middle of the imperialist darkness," the Libyan leader said, adding: "There is a fear that they would liquidate him as they liquidated Kennedy, Martin Luther King and Abraham Lincoln."
Gaddafi, who is the African Union chairman, had offered to work with Obama to sustain security, stability and prosperity in Africa and elsewhere.
Gaddafi praised Obama for breaking with what he said was the previous American foreign policy that dictated to the rest of the world what to do to serve U.S. interests.
"He (Obama) speaks logically. Arrogance no longer exists in the American approach which was previously based on dictating to the rest of the world in order to meet its own conditions," Gaddafi said in the remarks carried by state media.
Gaddafi, who took power in 1969 in a military coup in his oil- and gas-rich North African state, was shunned for decades by the West, which accused him of supporting terrorism.
His ties with Western countries have improved since Libya announced in 2003 it was scrapping weapons of mass destruction programs and agreed to pay compensation for families of victims of bombings of U.S. and French airliners.