"A lot of that toothpaste is already out of the tube. I never supported the deal in the first place. I thought it was a huge mistake, but the multilateral sanctions are done," Ryan said on NBC's "Meet the Press"
in a clip posted Friday.
Elaborating further, Ryan said it would be difficult to bring back the international community to a point where many countries would isolate Iran.
"I don't think you're going to go back and reconstitute the multilateral sanctions that were put in place," Ryan said.
The United Nations has so far not found Iran to be developing nuclear materials in violation of the agreement it signed with the United States, other permanent members of the UN Security Council and Germany.
Other countries party to the deal, including Iran, have said the US alone could not unravel the agreement, which involves a host of countries and has already pushed billions of dollars into Iran in exchange for it curbing its nuclear program.
President Donald Trump criticized the Iran deal during the campaign, but as of the first two weeks in office, he had not yet pulled the US out of the agreement.
Signaling his intent to take a tough approach on Tehran, his administration on Thursday put Iran "on notice" for testing a ballistic missile.
Then on Friday, the Treasury Department
imposed sanctions on the longtime US foe in response to the missile test.
Ryan said he supported the Trump administration's approach to Iran so far and that there was broad support in Congress for further sanctions. He said the US needs to "rachet up" sanctions where it can in response to Iran's sponsoring of terrorism and testing ballistic missiles, while also "rigorously" enforcing the nuclear deal.
"I think we should expend our effort where it can pay off the most," Ryan said. "What they're doing now makes a lot of sense."
Still, outside of Iran's reported cooperation with the nuclear agreement, Ryan criticized the country on a host of issues. He noted Iran is a state sponsor of terror and at odds with the US on many issues in the region.
"They are a belligerent force in the Middle East," Ryan said. "They write on the side of their ballistic missiles in Hebrew, Farsi and English, 'Death to Israel' and 'Death to America.' This is not a peaceful nation."
The speaker acknowledged Iran's closeness with Russia in "destabilizing" the region made the situation trickier.
Ryan took former President Barack Obama to task for what he viewed as an ineffective approach to Iran and the region, blaming Obama for Iran's missile tests and the situation in Syria.
Iran has so far largely dismissed the Trump administration's initial moves, standing by the agreement signed under the Obama administration. However, Iran did say it would respond in kind after Trump signed an executive order temporarily banning citizens from traveling to the US.