Detectives are visiting shops across the city centre where the untested highs, which mimic the effects of illegal drugs, are sold.
Retailers are permitted to sell the substances by labelling them as "plant food" or "bath salts".
However, shops are banned from selling potentially lethal legal highs to youngsters.
The crackdown comes after a teenage boy was rushed to hospital on THREE consecutive days after taking toxic legal highs.
Police today warned retailers they could be held responsible for youngsters becoming ill - or even dying - under "culpable and reckless conduct" legislation.
It is an offence to supply someone under 18 a substance if the seller knows the substance is likely to be taken to cause intoxication.
However, it can be difficult to prove a shopkeeper knows the substances sold will be taken.
Chief Inspector Alan Porte said: "I am concerned someone may take one of these substances and become very ill, or die.
"If officers could prove staff within a particular premises sold the substance knowing it was for human consumption, then we may report the matter to the procurator fiscal. Shopkeepers need to take responsibility for their actions."
Shops selling legal highs also must ensure the packets are marked "not for human consumption".
The 17-year-old hospitalised three nights in a row first collapsed on Friday night in the city centre and was taken to Glasgow Royal Infirmary.
The following day he was back in hospital after taking another suspected legal high. On Sunday, shocked medics had to treat him in hospital after he swallowed another substance.
Police said all three incidents took place in Union Street. It is not known where the teenager obtained the substances.
Officers were also called to a report of a disturbance near Union Street and found another 17-year-old male unconscious. It is believed he had also taken a legal high.
So-called legal highs can cause drowsiness, hallucinations, coma, paranoid states, seizures and death.
The Evening Times previously revealed how an increasing number of substances contain banned drugs, as well as amphetamines and tranquilizers.
Mr Porte, area commander for the city centre, said: "A significant proportion of these substances do contain controlled drugs.
"That means it is still an offence to take them whether you knew they have controlled substances in them or not. If controlled drugs are found, you will be subjected to the full rigour of the law."
The warning comes days after the Scottish Government held a summit with police, trading standards and Home Office staff in a bid to tackle the growing problem.
Justice Secretary Kenny MacAskill hosted the meeting in Glasgow which focused on how to disrupt the sale and supply of legal highs.
He warned: "Just because they are legal doesn't mean they are safe."
Earlier this month, we told how a 14-year-old boy was taken to hospital after taking a legal high.
In 2012, there were 36 deaths in Scotland where legal highs were found during the toxicology report - three times the death rate from ecstasy.
Substances sold as legal highs have similar effects to illegal drugs, but fall outside the UK government's misuse of drugs laws.