Friars Minor has launched an investigation into its finances dating back to 2003 after revealing it was concerned by the financial activities of some members.
The head of the order said in a statement the actions of outsiders had also caused a grave situation.
Bro Michael Perry says an oversight had meant the finances of the order had been compromised.
The general treasurer in the order's administrative offices has resigned.
There are around 15,000 members of the Friars Minor order worldwide.
Bro Michael said: "The General Curia finds itself in grave, and I underscore 'grave' financial difficulty, with a significant burden of debt.
"Second, the systems of financial oversight and control for the management of the patrimony of the Order were either too weak or were compromised, thus limiting their effectiveness to guarantee responsible, transparent management.
"We have initiated steps to address these concerns. Third, there appears to have taken place a number of questionable financial activities that were conducted by friars entrusted with the care of the patrimony of the Order without the full knowledge or consent of the former and current General Definitorium.
"Because of the scope and magnitude of these activities, they have placed the financial stability of the General Curia at grave risk."
He added: "I realise that many of you will be seriously disappointed and discouraged by this situation.
"It will also raise many questions for which you have a right to a response. I hope in time we will be able to provide more information.
"It is my intention to give a full account of the whole affair to the General Chapter.
"In the meantime, the General Definitorium and I call upon your prayer and support as we move forward with these matters and as we prepare for the 2015 General Chapter."