Donald MacLeod, head of leisure firm CPL, fears a roll-out of the policy could give the impression the city centre is a no-go area.
Bosses at The Arches have decided to stop anyone under 21 from attending club nights following the suspected drugs death of a schoolgirl.
Regane MacColl, 17, from Duntocher, Dunbartonshire, died in the early hours of Sunday, February 2, after becoming ill inside the club.
Mr MacLeod, who runs venues including the Garage, Tunnel, and Cathouse, said: "The main fear is that this would become an adopted policy and rolled out across the city.
"It would be a huge culture shock and would empty the streets of Glasgow. I also think it would drive drinking underground.
"I can see why they are doing it, but does it solve the problem? No.
"We have to look at the bigger picture. Drugs are out there and some kids may take them before they go into a venue."
Yesterday, the Evening Times told how former cop Graeme Pearson believes the strict age limit would "shift the problem elsewhere".
He believes targeting drug dealers would be more effective in preventing future deaths.
Mr Pearson, now a Labour MSP, said: "I understand why the club has done this, however, all they are doing is shifting the problem.
"If people are dealing drugs in a premises, that is what needs to be dealt with."
Police believe Miss MacColl's death may be linked to red 'Mortal Kombat' ecstasy tablets and issued a warning.
A 19-year-old woman, who had also been at the Arches, was admitted to the Glasgow Royal Infirmary the same night Miss MacColl became ill.
Detective Inspector Sharon MacGregor said: "I can't stress enough how dangerous drugs are. Illicit drugs are unstable, unpredictable and extremely dangerous as this outcome shows.
"Often the content of the drugs is unknown but they could contain dangerous chemicals and people need to understand the devastating effect they can have."
More than 1350 clubbers have already signed the anti-21 door policy petition.
The petition, called Get The Arches back to Over-18s, was posted online just hours after the club made the announcement. It reads: "Changing the age restriction will in no way tackle this matter."
The Arches said the under-21 ban starts immediately.