The motion was rejected with 67 votes in favour, 111 against and no abstentions.
M5S, the centre-left opposition Democratic Party (Pd) and leftist AVS voted in favour of the motion.
The centrist party, Azione, did not take part in the vote.
Santanchè, a leading member of Prime Minister Giorgia Meloni’s Brothers of Italy (FdI) party, has been facing calls to quit since investigative journalism programme Report on Rai 3 aired damning allegations.
The show alleged that companies linked to her failed to pay suppliers and dismissed workers without giving them redundancy payments and received COVID aid improperly.
During the debate the minister told senators she did not lie to parliament about a judicial probe against her.
“Even the newspapers have written that the formal notification of the investigation arrived at my residence on July 17,” she said.
“So, in the Senate I told the truth,” she continued, referring to a briefing to parliament on July 5 after the television report.
On that occasion, Santanchè told lawmakers she was not under investigation, stating she had not received notification of a probe.
She also claimed to have been the victim of “dirty, disgusting practices” by the media.
It subsequently emerged that she was under investigation for alleged false accounting and false bankruptcy in running the many companies in her Visibilia business galaxy.
On Monday, judicial sources said aggravated State fraud could also be added to the list of possible charges against her.
Santanche’ denies all wrongdoing.
ANSA