The classic work should be removed from school curricula, according to Gherush 92, a human rights organisation which acts as a consultant to UN bodies on racism and discrimination.
Dante's epic is "offensive and discriminatory" and has no place in a modern classroom, said Valentina Sereni, the group's president.
Divided into three parts – Hell, Purgatory and Heaven – the poem consists of 100 cantos, of which half a dozen were marked out for particular criticism by the group.
It represents Islam as a heresy and Mohammed as a schismatic and refers to Jews as greedy, scheming moneylenders and traitors, Miss Sereni told the Adnkronos news agency.
"The Prophet Mohammed was subjected to a horrific punishment – his body was split from end to end so that his entrails dangled out, an image that offends Islamic culture," she said.
Homosexuals are damned by the work as being "against nature" and condemned to an eternal rain of fire in Hell.
"We do not advocate censorship or the burning of books, but we would like it acknowledged, clearly and unambiguously, that in the Divine Comedy there is racist, Islamophobic and anti-Semitic content. Art cannot be above criticism," Miss Sereni said.
Schoolchildren and university students who studied the work lacked "the filters" to appreciate its historical context and were being fed a poisonous diet of anti-Semitism and racism, the group said.
It called for the Divine Comedy to be removed from schools and universities or at least have its more offensive sections fully explained.
The remarks prompted Italian cultural associations, actors who have performed the epic and even gay groups to rush to the defence of the poet.
It was wrong to judge Dante by the standards of today, said Giorgio Rembado, the president of an Italian head teachers' association.
"Works of literature need to be placed in the historical context," he said.
Banning the Divine Comedy would be "senseless".
Franco Grillini, the head of Gaynet, a gay rights' organisation, said the suggestion that Dante's writings should be prohibited marked "an excess of political correctness"
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