Officers will circulate secret intelligence among city hoteliers in a bid to crack down on prostitution, theft and serious fraud.
And a top city cop has one message for anyone planning to commit a crime at a Glasgow hotel: Stay at home or sleep in the cells.
Inspector Gavin Smith, who is based in the city centre, said: "Hotels might be in competition for their guests but not for criminals.
"But Police Scotland has a different kind of accommodation ready for criminals."
Hotel Check-In Glasgow will focus on creating a detailed picture of habits of the individuals involved in serious organised crime.
It is hoped sharing information about criminal customers will prevent them moving between hotels.
CCTV of suspects and known criminals will also be circulated, as part of a deal between Police Scotland and city hotels to share information.
Inspector Smith said: "The Check-In system is a real bonus for Police Scotland and Glasgow hotels.
"It allows linked hotels and police to share real time information and CCTV 24/7.
"We'll be targeting sneak-in thieves, credit card fraudsters, pickpockets or anyone else who thinks hotels are an easy target."
Official figures reveal officers have recorded more than 130 crimes and offences at hotels in Glasgow city centre, since April, last year.
Senior officers hope the scheme will enhance "public image and reputation of Glasgow" to potential visitors ahead of the 2014 Commonwealth Games.
Inspector Smith added: "Glasgow is well-known for being visitor-friendly.
"We want to build on that and work with local hotels to keep guests, staff and the city safe."
Hotel Check-In Glasgow is funded by Police Scotland and the Greater Glasgow Hotels Association.
The scheme comes afer the Evening Times revealed hotels guests are being targeted in a phone scam aimed at conning people out of their cash.
Unsuspecting guests at hotels in Glasgow were duped into revealing their bank details by fraudsters posing as hotel workers.
Police believe the scam is linked to a spate of incidents across the city centre.
Officers warned people to be on guard and to never reveal card PIN numbers, bank or personal financial details - especially over the phone.