The girl brought in the Nicorette mouth spray – prescribed to help her kick her addiction - and shared it with a group of Year Seven and Eight pupils at lunchtime.
Parents at Wolstanton High School, in Newcastle-under-Lyme, in Staffordshire, then received calls to say 20 of the children had been violently sick.
The pupils who tried the spray suffered vomiting, dizziness and headaches. One needed hospital treatment.
One unnamed mother - whose 12-year-old son was among those who felt unwell - told the local paper: "When he was collected he was extremely pale, holding on to the rail outside and some of the others had been sick.
"He's suffered a toxic overdose. Apparently 20 children were affected."
Alan Aston, principal of Wolstanton High School, described the incident as a 'one-off' and said teachers acted swiftly to inform parents about what had happened.
He added that the girl had since been disciplined.
He said: "The spray was shared with other pupils and they became nauseous. We have dealt with the pupil involved using our own sanctions.
"We already have procedures in place to protect pupils but unfortunately this was a prank that went wrong."
Mr Aston also defended the school's decision to signpost children to the NHS's Time to Quit, where the pupil was prescribed the Nicorette spray.
He said: "All of our pupils are under 16 and smoking is illegal, which we take very seriously.
"What happened with this case was a pupil followed our advice and went on an NHS course.
"The spray was prescribed and brought into the school in a regrettable incident."
Ian Saberton, Time to Quit service manager, said staff had followed the proper procedures when prescribing the spray.
He said: "Time to Quit has recently started to provide stop smoking support to pupils at Wolstanton High School.
"All pupils who request support receive an appointment after which they are required to do some preparation for a quit attempt, medication is only recommended at the following appointment.
"All Nicotine Replacement Therapy products are licensed for people aged 12 years and over and are available on general sale.
"All protocols for stop smoking support had been followed in this case."