Foreign ministry spokesman Bahram Ghasemi called the accusations that Tehran lied about its nuclear ambitions "worn-out, useless and shameful".
Netanyahu's comments came from a "broke and infamous liar who has had nothing to offer except lies and deceits," Ghasemi said in a statement.
"Netanyahu and the notorious, child-killing Zionist regime must have reached the basic understanding that the people of the world have enough awareness and cognisance," he added.
Netanyahu said in an elaborate televised presentation on Monday that he had new "proof" of an Iranian nuclear weapons plan that could be activated at any time.
But he did not provide evidence that Israel's main enemy had actively worked to obtain an atomic weapon since the 2015 agreement between Tehran and six world powers.
His accusations came as the United States considers whether to pull out of the atomic accord with Tehran.
Iran has always denied it sought a nuclear weapon, insisting its atomic programme was for civilian purposes.
On the streets of Tehran, driver Seyed Ahmad Moghadasi rejected Netanyahu's statements as "ridiculous" and doubted the US would pull out of the nuclear deal.
US President Donald Trump "will stay because 99 percent of the world has accepted (the agreement). The remaining one percent - that's Netanyahu and Trump - aren't worth anything in the face of the whole world," he said.
But Alireza, an office worker, didn't share such optimism.
The gamble of Iranian President Hassan Rouhani in backing the nuclear deal has failed to pay off, he said, leaving Tehran "besieged" by Washington.
"I think that a war could break out in some time" against his country, Alireza said, worried by the deployment of US forces around Iran.
