Pupils at Pingle School, Swadlincote, were asked to send naked images to the messaging site ooVoo.
Derbyshire Police said it was "investigating the sharing of indecent images" via text message, social media, or tablet and phone apps.
The force said it was unclear who made the requests. The school said warnings were sent to parents and other schools.
Simon Waller, assistant head at the school, said: "It came to light after one of our mentors had seen a text message and was quite suspicious.
"It started off quite low key but the more we dug, we uncovered quite a big problem.
"We've got a really rigid e-safety programme. Clearly some of the messages aren't getting through, so we have got extra measures in place."
He said police officers were coming in to deliver assemblies on online safety to all year groups. Pupils are aged from 11 to 18 years old.
A Derbyshire Police spokesperson said the investigation was in an early stage and it was not yet known whether requests were sent by a lone online predator.
Police have urged parents to be vigilant and monitor their child's online activity.
A spokesman for ooVoo said the issue was a problem for the social media industry and the site aimed to provide users with a "safe and private experience".
He said: "We take these issues very seriously and have a chief privacy officer who roots out and deletes any accounts which may place children or any ooVoo users at risk.
"The reported behaviours are offensive, illegal and when identified as such will be immediately reported to the proper authorities."

Eighteen people were arrested during the four-day operation and 63 vehicles were seized.
Forty-two of the vehicles had no insurance and/or licence.
A further 21 had no Vehicle Excise Licence, the Hampshire and Thames Valley operation discovered.
Hampshire Constabulary and Thames Valley Police said the joint operation earlier this month aimed to make the roads safer for people living and working in the region.
The "large quantity" of the substance believed to be cocaine was discovered in a car in the Iver and Denham area, officers said.
Other items seized included a stolen digger worth £12,000.
The lorry driver asleep in his cab was in a vehicle "piggy-backing" another vehicle in Portsmouth.
Both drivers were given fines totalling £1,000.

She may continue to exercise some functions, but her role will be very limited.
Sinn FÃ©in has seven days to re-nominate a new deputy first minister following Mr McGuinness' resignation.
However, the party is adamant it will not replace him.
From the evening of Monday 16 January, the baton passes to Northern Ireland Secretary James Brokenshire. The law says he shall call an election.
The usual time period for an Assembly election campaign is six weeks. If Mr Brokenshire moved immediately, then voters in Northern Ireland would be going to the polls in seven weeks' time.
However, a previous court case indicated that the Northern Ireland Secretary did not necessarily need to call an Assembly election immediately, but within a reasonable period of time.
Mr Brokenshire could use this flexibility to allow for more negotiations.
What he cannot do as the law stands is suspend the Stormont Assembly and Executive.
That power was used by previous governments on a number of occasions, but it was removed from the statute book as part of the 2006 St Andrew's Agreement.
It would require a fresh emergency law to be passed by Westminster for suspension to be used again in the future.
During the 2015 crisis over welfare reform and IRA activity, the Northern Ireland Office was adamant that, in the event of a breakdown, it would not try to bring back suspension powers, but allow fresh elections to take place.
Government sources indicate that thinking has not changed, even though a potentially polarising campaign might not make the restoration of devolution in spring any easier.
Sinn FÃ©in say their rift with the DUP is far wider than the latest Renewable Heat Incentive  scandal.
But whilst the Stormont parties go into election mode, it seems unlikely there will be any progress on either recouping the potential RHI losses, or agreeing an independent investigation into the affair.
Police are investigating after pupils at a Derbyshire school were encouraged to post explicit images online.
[NEXT_CONCEPT]
A lorry driver asleep at the wheel and a car thought to be carrying £100,000 of cocaine were among the discoveries made during a police crackdown on motoring offences.
[NEXT_CONCEPT]
Once Martin McGuinness' resignation takes effect, under the joint protocols that govern Stormont's power sharing government, First Minister Arlene Foster also loses her office.