In a post on Truth Social on Tuesday, Trump urged that "someone please tell Pope Leo" about the killings of protesters by Iran and that "for Iran to have a Nuclear Bomb is absolutely unacceptable".
The US and Israel attacked Iran on February 28.
Iran responded with its own strikes on Israel and Gulf states with US bases.
US-Israeli strikes on Iran and Israeli attacks in Lebanon have killed thousands and displaced millions.
Iran does not have nuclear weapons while the US does.
Israel is widely believed to be the only Middle Eastern country with nuclear weapons.
While Western countries have long believed that Iran wants a nuclear bomb - or at least the ability to make one very quickly - Tehran has always denied that, citing its membership of the Nuclear Non-Proliferation Treaty.
Trump's comments come after Pope Leo warned earlier in the day of the risk of democracies sliding into "majoritarian tyranny".
The first US pope, Leo wrote in a letter issued by the Vatican about the use of power in democratic societies, and said democracies remained healthy only when they were rooted in moral values.
The Pope has criticised Trump's decision to launch the war against Iran, saying God rejects the prayers of those who launch wars and have "hands full of blood".
The Pope termed Trump's threat in April to destroy the Iranian civilisation as unacceptable and previously declined to join the US president's so-called "Board of Peace" initiative for Gaza.
The religious leader has also urged a "deep reflection" on the way migrants are treated in the US while Trump has pursued a hardline immigration policy.
On Sunday, Trump called the Pope "weak" and "terrible" on crime and foreign policy issues.
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