"I think if people want to flirt with Iran, they should take a look at what the consequences might well be for them. And we hope that they will think twice and we will support them if they do," the chief US diplomat said.
During a question-and-answer session at the State Department's public policy forum on Latin America, Clinton said it was a "very bad idea for the countries involved" to allow Iran to establish itself in the region.
In a sign of Iran's push for closer ties with the mostly leftist governments thriving at the doorstep of the United States, Iranian President Mahmoud Ahmadinejad visited Venezuela, Bolivia and Brazil last month.
"We hope that there will be a recognition that this is the major supporter, promoter and exporter of terrorism in the world today," Clinton said.
In May, she defended moves by President Barack Obama's administration to engage anti-US leaders in Latin America as a way to check what she called "disturbing" Iranian and Chinese inroads in the region.
Clinton said Obama had to take a new tack after his predecessor George W. Bush's efforts to isolate such leaders had only made them "more negative" toward Washington and more receptive to rival powers.
In "a multipolar world where we are competing for attention and relationships with at least the Russians, the Chinese, the Iranians," such countries can fill the void left by the lack of US engagement, she warned.