In her first public comments since the weekend release of the classified State Department cables, Clinton said on Monday that Wikileaks acted illegally in posting the material.
"I will not comment on or confirm what are alleged to be stolen State Department cables," Clinton said.
"But I can say that the United States deeply regrets the disclosure of any information that was intended to be confidential, including private discussions between counterparts or our diplomats' personal assessments and observations.
"I want to make clear that our official foreign policy is not set through these messages, but here in Washington," the top US diplomat added.
She said the Obama administration was "aggressively pursuing" those responsible for the leak.
Despite the damage, Clinton said she was "confident'' that US partnerships would withstand the challenges posed by revelations.
"Our policy is a matter of public record as reflected in our statements and our actions around the world.
"I would also add that to the American people and to our friends and partners, I want you to know that we are taking aggressive steps to hold responsible those who stole this information," she said.
The White House has directed US government agencies to tighten procedures for handling classified information after the mass leak.
The new procedures would ensure "that users do not have broader access than is necessary to do their jobs effectively," a directive from the Office of Management and Budget said on Monday.
"The recent irresponsible disclosure by WikiLeaks has resulted in significant damage to our national security," Jacob Lew, the director of the office, said.
"Any failure by agencies to safeguard classified information... is unacceptable and will not be tolerated."
WikiLeaks on Sunday began releasing a quarter of a million confidential US State Department cables, detailing diplomatic activities around the world in what the White House has called a "reckless and dangerous action."
US officials have not confirmed the source, but suspicion has fallen on Bradley Manning, a former army intelligence specialist arrested after the release of a video showing air strikes that killed reporters in Iraq.
The US also launched a criminal investigation into the release of hundreds of thousands of US diplomatic documents by the website WikiLeaks.
Eric Holder, the US Attorney General, said on Monday that there is an "active and ongoing criminal investigation," and that the website's chief would be pursued if he were found to have broken the law.
"We are not in the position, as yet, to announce the result of that investigation," he said, adding that the justice and defence departments were both probing the website.
"This is not saber-rattling," Holder said when pressed by reporters over what action the US could take against WikiLeaks founder Julian Assange, who is believed to be based in Europe.
"To the extent that we can find anybody who was involved in the breaking of American law... they will be held responsible," Holder said.
"To the extent there are gaps in our laws, we will move to close those gaps. It is not the case that anybody at this point, because of their citizenship or their residency, is not a target or the subject of an investigation."
A day after the release of the cables, Mahmoud Ahmadinejad, the Iranian president, questioned the credibility of the information contained in the diplomatic memos.
According to the memos released on Sunday, King Abdullah of Saudi Arabia repeatedly urged the US to attack Iran to destroy its nuclear programme to stop Tehran from developing a nuclear weapon.
'Psychological war game'
Commenting on the leak, Ahmadinejad accused the US government of pursuing a strategy resembling "an intelligence and psychological war game". He asserted it was aimed at having a "political impact," but would fail.
"Nations are aware. Such a game will have no effect. It's so worthless that it isn't worth someone referring to them or wasting time to refer to them," the president told reporters in Tehran.
He alleged the leaks were an "organised" effort by the US to stir trouble between Iran and its Arab neighbours.
Arab nations just across the Gulf are known to be wary of Iran's rising regional influence, military power and nuclear activity. The leaked documents, however, reveal a much higher degree of alarm in the calls for US military action.
The US has helped several Arab nations in the Gulf increase their anti-missile defences and itself has a naval presence in the region.
Binyamin Netanyahu, Israel's prime minister, said the leaked memos provided clear proof that the Arab world agreed with his country's assessment that Iran was the chief danger to the Middle East.
The Saudi king was just one of many Arab voices in the documents calling for tough action against Iran - proof that Israel was not alone in its belief that Tehran was a growing menace to the region, Netanyahu said.
"The chief danger to world peace comes from the Iranian regime's arming and aggression. The important thing is...that more countries, governments and leaders in the Middle East and in the world's wider area understand that this is the fundamental threat," the prime minister added.
He also suggested that a unified front with Arab nations against Iran could bring a "breakthrough" in efforts to bring peace to the region.
Israel has long considered Iran the top danger in the Middle East, citing its development of medium-range missiles capable of striking Israel, its support for militant groups such as Hezbollah and Hamas, and most critically, its suspect nuclear programme.
The West, and many Arab countries, believe that Iran is developing nuclear weapons. Iran denies the charge.
Russian TV ignored mentions about the country in the leaks. That could be because the cables showed US diplomats characterising the country as a "virtual mafia state."
They also said Dmitry Medvedev, the Russian president, was relatively powerless in the shadow of Vladimir Putin, the prime minister.
The US embassy reportedly referred to Putin as an "alpha dog" who made all the decisions. It vividly added that Medvedev - who one dispatch said often looked indecisive and pale - simply "plays Robin to Putin's Batman."
Italian papers widely reported that the leaked documents included the comments that Silvio Berlusconi, the Italian prime minister "appears increasingly to be the mouthpiece of Putin" in Europe.
They said the documents noted that the two men had a "extraordinarily close relationship, made up of generous gifts and lucrative contracts".
Elizabeth Dribble, the former number two at the US embassy in Rome, described Berlusconi in internal memos to Washington as "incompetent and vain".
She noted that he was "a leader physically and politically weak, tired from too many parties".
Italians on the streets of Rome shrugged their shoulders and laughed over revelations about Berlusconi and their foreign minister said the prime minister was not offended.
James Walston, a political analyst from the American University of Rome, said that there was nothing in the comments on Berlusconi that would surprise anyone regularly reading Italian newspapers, although he added that it was embarrassing for a diplomat to be seen as un-diplomatic.
Walston said that although Berlusconi may be taking the leaks lightly it "undermines his position on the world stage".