All the luggage had to be taken off as the bomb squad was called in with sniffer dogs, the MailOnline reported.
Nothing was found and the plane was eventually allowed to leave at 9.25am.
The "joke", said the police, had not been appreciated by either the airline or the passengers, many of whom had been extremely worried by the threat.
One of the men at least will face prosecution as it is an offence to cause a false bomb scare. A full investigation is underway and a preliminary report has already been sent to the local prosecutor's office.
A Ryanair spokesman said: "The crew of this flight from Brussels to Madrid (2 Sep) requested police assistance after a number of passengers became disruptive prior to departure. Police removed and detained the individuals before the aircraft departed to Madrid.
"We will not tolerate unruly or disruptive behaviour at any time and the safety and comfort of our customers, crew and aircraft is our number one priority.
"This is now a matter for local police."
In March 2016, both the Brussels-Zaventem airport and the city's metro were the subject of separate terrorist attacks that killed 32 people.