During her university years, De Gregorio entered the field of journalism, working at local radio and television stations in the region.

In 2001 she published Non lavate questo sangue ('Don't Wash This Blood'), an account of the turmoil that surrounded the 28th G8 summit in Genoa, and an article for the literary journal Adelphi.

The magazine Prima Comunicazione prematurely released excerpts from an interview in which she revealed that she had accepted an offer from Renato Soru, the new owner of l'Unità, to become the daily's editor.

When the publishing company owning the paper went bankrupt, as managing editor De Gregorio was subjected to joint liability claims in connection with defamation lawsuits filed against the newspaper in civil court (although she wasn't the writer of the content at issue).

[10][11] On 25 April 2010, De Gregorio was honored with the Renato Benedetto Fabrizi prize by the Associazione Nazionale dei Partigiani d'Italia.