The 62-year-old conservative former premier was favourite at the start of the year to win the French presidency after clinching the nomination for the Republicans party in November.
"Going down this dead-end street is taking the state, our faith in democracy and its fellow travellers hostage", de Villepin wrote in Le Figaro newspaper.
Replacing him as Republican nominee at this late stage would be a big gamble for the party, but having a candidate under investigation could also backfire.
"I have chose to end my role as spokesman of Francois Fillon", Thierry Solere, also the organizer of the right-wing primary in which Fillon had secured a landslide victory over Alain Juppe, said on his Twitter account. In an unusual statement, the Court of Cassation said the judicial system needs neither support nor criticism because "judges follow their own rhythm in full independence. and are duty-bound not to engage in the electoral debate". "It seems to me that today only he (Juppe), with all his experience, can carry the flame".
French presidential hopeful Marine Le Pen was asked to attend a meeting with a judge over accusations that she created fake European Union parliament jobs for members of staff.
"The right-wing and center camps. have to be united behind him", a source in Juppe's camp told the French news agency AFP.
The race for the French presidency is stepping up a gear this weekend with current polling suggesting the two movements that have dominated French politics since the 1950s are unlikely to get a candidate into the decisive second round of voting.
François Hollande and Marine Le Pen are shown in the foreground of a 2012 ceremony in Montauban France
"I won't give in, I won't surrender and I won't withdraw", Fillon said, claiming he was the target of a "political assassination".
Fillon's troubles have benefited centrist independent candidate Emmanuel Macron, who on Thursday announced his policy platform, including boosting European unity and combating populism and corruption.
Analysts say Fillon is benefiting from the split between party supporters and defectors by becoming the "default" candidate.
Lawyers for Fillon and his wife Penelope would not comment on the search.
A new voter survey out Thursday showed Macron scoring 24 percent, ahead of Fillon's 19 percent in the first round of the election.
Ms Le Pen is now running to be French president. He said Thursday he'd do without those who left his campaign, insisting the base is holding and has planned media appearances after the weekend, including an hour-and-a-half-long interview on Europe 1 radio on Monday morning.
The independent Macron has expressed his desire to create a "roadmap" to fight Islamic extremism and terrorism, coming from the Mideast and Africa, better, while also calling for increasing military spending to up to 2% of the GDP - something which the USA and North Atlantic Treaty Organisation allies have always been demanding of France.
United States airstrikes conducted in Yemen overnight
Conducted in partnership with Yemen's government, the strikes were coordinated with President Abd Rabuh Mansur Hadi, Davis said. The officials spoke on condition of anonymity because they weren't authorized to speak to.