Hegseth, in a post on X, said the United States had carried out the strikes on Sunday in international waters in the eastern Pacific, targeting two boats "carrying narcotics" with three people on board each.
"All 6 were killed. No U.S. forces were harmed," he said.
As in previous strikes, which began under President Donald Trump's administration in September, US officials did not release the identities of those killed.
The administration has released no firm evidence that the boats have been smuggling narcotics or posed a threat to the United States.
Experts say the strikes, which have taken place in both the Pacific and Caribbean, amount to extrajudicial killings even if they target known traffickers.
Hegseth said the two vessels were "operated by Designated Terrorist Organizations," but did not name the groups.
The Trump administration has said in a notice to Congress that the US is engaged in "armed conflict" with Latin American drug cartels, describing them as terrorist groups as part of its justification for the strikes.
Video accompanying Hegseth's post on Monday showed a strike on one boat sitting stationary in the water, and a separate open-top vessel exploding while underway.
A short video clip in color of the moving vessel shows what appears to be several parcels loaded inside. No details can be made out on the stationary vessel, which appears in black-and-white video.
The US strikes have now destroyed at least 20 vessels so far -- 19 boats and a semi-submersible.
"Under President Trump, we are protecting the homeland and killing these cartel terrorists who wish to harm our country and its people," Hegseth said.
- 'Strong indications' of rights violations -
Critics of the operation say the deadly strikes violate international law, while families of some of those killed said they were fishermen.
Two people have survived the strikes and been repatriated to their home countries of Ecuador and Colombia. None have been charged with a crime.
Historically, the United States has sought to capture boats believed to be trafficking drugs. Ferrying narcotics itself is not a capital offense under US law.
The United Nations has urged Washington to halt the strikes, with UN rights chief Volker Turk on Monday saying there are "strong indications" they violate international human rights law.
"I have called for investigations by the US administration first and foremost, because they need to... ask themselves the question: are these violations of international human rights law? Are they extrajudicial killings?" Turk told AFP.
"I mean, there are strong indications that they are, but they need to investigate this," he added.
The strikes on alleged drug traffickers have coincided with a US military buildup in the Caribbean.
In addition to six Navy ships already in the region, the USS Gerald R Ford carrier strike group is set to arrive in the coming days.
Washington says their mission is to combat drug trafficking, but Caracas views the ships as a threat to oust Venezuelan leader Nicolas Maduro.
des/fg
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