But she said despite those concerns being raised, North Korea in response had "offered only an insistent refusal to recognise that [it] has been on the wrong course."
North Korea itself hit out at Clinton shortly before she spoke, saying that six-party talks on its nuclear programme were "dead" and calling Clinton an unintelligent, "funny lady".
Clinton has been holding a series of meetings with Asian diplomats at the Phuket meeting Asean Regional Forum in an effort to enforce the latest UN sanctions ordered in the wake of North Korea's recent nuclear and missile tests.
The sanctions triggered an angry response from North Korea, which announced several weeks ago it was abandoning the six-party disarmament talks and scrapping all agreements it had reached in them.
Speaking to reporters, Clinton outlined a possible approach to North Korea, including a renewed drive to push the North into "full and verifiable denuclearisation", saying the US was prepared to offer in return "significant energy and economic assistance."
Nonetheless she said there would be no compromise until North Korea completely gave up its atomic drive.
"In short our approach isolates North Korea, imposes meaningful pressure to force changes in its behaviour and provides an alternative path that would serve everyone's interests," Clinton said.
While the initial effort was focusing simply on restarting negotiations, she said there would be no reward for North Korea "just for returning to the table".
Earlier US officials said Clinton's statement was intended to present North Korea with a "stark choice" between further isolation and sanctions, or a return to engagement with the international community.
A member of North Korea's delegation attending the Phuket forum said the suggested US incentives for denuclearisation were "nonsense", blaming the "deep-rooted hostile policy" of the US for the current crisis.
"How could the US talk about a package deal without abandoning its hostile policy and guaranteeing security and peace for us"
North Korean foreign ministry
"The six-party talks are already dead," Ri Hung-sik, director-general of the North Korean foreign ministry's international organisation bureau, told South Korea's Yonhap news agency.
"The United States must abandon its hostile policy immediately, then talks would be possible."
"How could the US talk about a package deal without abandoning its hostile policy and guaranteeing security and peace for us?" Ri was quoted as saying.
Clinton had earlier raised concerns at growing ties between North Korea and military-ruled Myanmar, including the possible transfer of nuclear technology to the Southeast Asian nation.
She said growing military ties between the two countries had the potential to threaten regional stability.
On Wednesday, Clinton said her counterparts from Japan, Russia, China and South Korea - all parties to the six-party talks on North Korea - had agreed on the need to enforce still tighter sanctions if Pyongyang refuses to take certain key steps.
Those include dismantling the North dismantling its nuclear reactor at Yongbyon and giving up its plutonium stockpile.
"All four of the other foreign ministers agreed that full implementation is important to demonstrate unanimity and resolve in the face of North Korean provocations and to make clear that complete and irreversible de-nuclearisation is the only viable path for North Korea," Clinton told reporters.
China, which has hosted the six-nation talks and is North Korea's biggest supplier of aid, said it was in close touch with all parties and it was important to take a long-term view of the disarmament process.
"Although the talks have come across some difficulties, one must not ignore the fact that major progress was acheived some time ago," said Yang Jiechi, the Chinese foreign minister.
"So one should take a long term point of view and work for the resumption of the six party talks."
On Wednesday, the US Senate called North Korea a "threat" to its neighbours and pushed for a formal review to see whether the Obama administration should return it to a US terrorism blacklist.
The previous US administration removed North Korea from the list in October 2008 as part of Washington's stop-start diplomacy with the country.