Keir Starmer has urged Iran not to retaliate as world leaders fear a response to a barrage of Israeli strikes overnight.
Israel launched three waves of air strikes early on Saturday, explicitly linking them to missile strikes from Tehran earlier this month.
Israel had made no secret of its plans to hit back against Iran, which it also blames for backing Hamas in Gaza.
As the world anxiously awaits Iran’s response, the prime minister warned of the need to ensure tensions do not escalate across the region.
The US also said Israel’s overnight strikes should end the direct exchange of fire between the two countries and warned Tehran of “consequences” if it responds.
Speaking at a press conference in Samoa, Sir Keir said: "I am clear that Israel has the right to defend itself against Iranian aggression and I am equally clear that we need to avoid further regional escalation and urge all sides to show restraint.
"Iran should not respond,” he added. “We will continue to work with allies to de-escalate the situation across the region."
A Number 10 spokesman said on Saturday morning the Government supports "Israel’s right to self-defence and to protect itself in line", so long as it adheres to "international humanitarian law".
Israel has said the attacks did not target nuclear or oil facilities, while Iran said the targets were military bases in Ilam, Khuzestan and Tehran provinces.
Israel said its aircraft struck "missile manufacturing facilities used to produce the missiles that Iran fired at the state of Israel over the last year".
A statement added that the airstrikes caused "limited damage".
In a pre-recorded video statement shared on social media early on Saturday morning, Israeli military spokesman Rear Admiral Daniel Hagari said: "The regime in Iran and its proxies in the region have been relentlessly attacking Israel since October 7 ... including direct attacks from Iranian soil."
"Like every other sovereign country in the world, the state of Israel has the right and the duty to respond."
The US said in a statement that Israel’s latest attack on Iran should now "complete" the exchange of fire between the two arch-enemies.
US secretary of defence Lloyd J Austin III spoke with Israel’s minister of defence Yoav Gallant, reaffirming America’s commitment to Israel’s security and right to self-defence.