A number of people were taken to hospitals across the city after the Northern Ireland Ambulance Service responded to the incident on Thursday night.
Doctors were put on standby at the Ulster, Mater and Royal hospitals.
A total of 15 people have been admitted to hospital - 11 at the Royal and four at the Mater. They are in a stable condition and are being kept overnight.
Dr Russell McLaughlin, consultant at the RVH A&E, told UTV the patients' symptoms were "consistent with drug and alcohol misuse".
Earlier, an NIAS spokesman said they dealt with casualties "at varying levels of consciousness".
A spokesperson confirmed that around 40 people were treated outside the complex, where a dance event headlined by Dutch DJ Hardwell was taking place.
John McPoland, from the Northern Ireland Ambulance Service, said they were alerted by staff at the SOS bus after a number of people arrived at the scene intoxicated, shortly after 8pm.
"We arrived down at the scene and assessed and very quickly declared a major incident because of the numbers of people involved," he said.
"It seems that a lot of the young people tonight have turned up already with lots of alcohol on board."
He said a couple of people were unconscious at the scene.
As with any concert, the safety of our patrons is our absolute priority at all times and we are very confident that we have sufficient staff on site to maintain a safe and enjoyable concert.
Odyssey General Manager, Adrian Doyle
A statement issued by Odyssey Arena General Manager Adrian Doyle said: "We are aware that a major incident has been declared by the Northern Ireland Ambulance Service outside the Odyssey Complex.
"It is our understanding that a number of patrons arriving at the Odyssey Arena to attend a concert by Dutch DJ act 'Hardwell' have required medical attention, having arrived intoxicated at the Odyssey Complex.
"These patrons were not granted entry to the Odyssey Arena, and were treated by the Ambulance Service outside."
He said the concert continued "as normal inside the Odyssey Arena."
Meanwhile, Pubs of Ulster "strongly condemned the events".
"We are extremely concerned to hear that a large number of young people are being treated for the apparent effects of alcohol and drugs," Chief Executive Colin Neill said.
"Pubs of Ulster would reiterate that alcohol should be consumed responsibly and safely. Pre-loading at home before going out is dangerous and can lead to unintended consequences with people putting themselves at great risk.
"Parents must stop under 18s getting access to drink and licensees should check ID and exercise extreme caution at all times."
It is understood doors to the over 16s event opened at 6.30pm.
Emergency services remained on stand-by after the concert ended.
Pauline O'Boyle, from Waterfoot in Co Antrim, took her two sons aged 16 and 17 to the concert, but returned after hearing reports of the major incident.
"As we arrived, we were quite concerned, about the ones that we had seen, you kinda knew to look at them, they were on something, either drink or drugs or something," she said.
"There were girls being carried out, that were just completely out of it, there were boys inside the Odyssey itself fighting with people, it was just not nice.
"I didn't expect this, it's quite scary as a parent."
An emergency number for anyone seeking information has been set up on 028 90 638131.