Meloni, leader of the far-right Brothers of Italy party and premier since October 2022, has often sought to act as a bridge between European and US positions.
"It is undeniable that we are experiencing a particularly difficult moment in relations between Europe and the United States," Meloni, who is close to US President Donald Trump, told parliament.
Trump's outrage at NATO allies for not joining the Iran war has prompted fears he would pull the United States out of the military alliance set up after World War II.
"What we call the West stands on two legs, the European leg and the North American leg," Meloni said in a wide-ranging address to the lower Chamber of Deputies.
"If the two legs do not move in the same direction, the West is doomed to paralysis and ultimately to irrelevance."
Meloni said her coalition government was "stubbornly Western because only if the West is united can it be a force capable of making its voice heard on the world stage."
She said she had voiced disagreements with the United States when they came up, such as over tariffs and in defending the importance of NATO.
"We must work to keep the two shores of the Atlantic united," in strengthening NATO and in encouraging Europe to stand on its own feet and "assume its responsibilities," she said.
Italy was pushing Brussels for a "balanced strategic autonomy that gradually reduces our dependencies, and for a defence capability that does not leave us dependent on our American allies," said Meloni.
