Meloni, head of the Brothers of Italy party, said Musk was exercising his right to free speech.
Musk – a billionaire ally of US President-elect Donald Trump who is set for a role in the incoming administration – has sparked anger across Europe with a string of attacks on the continent's leaders, including German Chancellor Olaf Scholz and UK Prime Minister Keir Starmer.
Meloni rejected a suggestion that Musk's comments on his X social network constituted "dangerous interference."
"The problem is when wealthy people use their resources to finance parties, associations and political exponents all over the world to influence the political choices of nation states," Meloni told reporters at a yearly press conference.
"That's not what Musk is doing," she insisted.
"Elon Musk financed an election campaign in his country, by his candidate, in a system in which, by the way, I would point out that this is quite common," she said.
"But I am not aware of Elon Musk financing parties, associations or political exponents around the world.
"This, for example, is what George Soros does," Meloni alleged.
"And yes, I consider that to be dangerous interference in the affairs of nation states and in their sovereignty," she said.
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Reviled by conservatives, and often the target of anti-Semitic conspiracies, Soros used wealth amassed as a financier in the 1970s and 80s to create the Open Society Foundations (OSF), which support a broad range of causes and NGOs worldwide, ranging from good-governance and democracy-building programmes to liberal public policy initiatives.
He has been a major donor during US elections but does not own a social media network or hold a position in government.
'Not left-wing'
"Is the problem that Elon Musk is influential and rich or that he is not left-wing?" queried Meloni, who has described Musk as a "genius".
She slammed "those who until yesterday described exponents of big finance – who often bet against nation states, who finance exponents of political associations – as fine, as philanthropy."
Meloni said she had not taken any money from Musk, "unlike those who have taken it from Soros."
She also denied media reports that her government is on the cusp of signing a controversial cybersecurity deal with Musk's company SpaceX.
Meloni said she refrained from commenting on other countries' domestic politics herself but had herself repeatedly been the victim of attacks.
She compared "left-wing" outrage over Musk's vocal support for the extreme-right Alternative for Germany (AfD) ahead of elections there with "left-wing" silence over what she said was "interference" by top German politicians in Italy's 2022 general election.
Twice during the press conference Meloni referred to Musk as Donald Trump by mistake.
Musk's political initiatives are intimately linked to his economic interests, experts suggest.
He is an enthusiastic supporter of Meloni – Italy's most right-wing leader since 1945.
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