Plants were ripped up, pots smashed and an attempt was made to set on fire a climbing frame and nappy bin.
Dirty nappies were also thrown across the play area at the Red Road Family Centre in Barmulloch, Glasgow.
The incident happened at some point over the weekend and it was discovered when staff opened the centre on Monday morning.
Kathleen McGuckin, childcare manager at the nursery and after school care centre, said: "We have been out all morning trying to clean up the mess.
"Our main worry is that they are going to come back and try and finish the job.
"It's the fact that our children have planted all their own flowers and they have just thrown them about.
"I have had to take the den off our climbing farm, which cost us £500.
"They tried to burn the nappy bin and they have been throwing the nappies about. It was a mess.
"The children are really upset and angry.
"We are a charity and a lot of the things that were damaged we had to apply for funding to get.
"It's not easy to replace things."
Kathleen said that in her 16 years of working at the nursery she has never experienced any vandalism as bad as this.
But she said the community around the nursery has rallied round and she has received messages of support and offers of help.
She added: "The response has been overwhelming with people saying they are wanting to help.
"North Glasgow Homes contacted us after seeing a post we put on Facebook and they stepped in to help us make the area secure, which is great."
North Glasgow Homes regeneration manager Margaret Layden said: "When we read the news on Facebook we wanted to help so we got in touch to see what we could do.
"We have been doing a lot of work with the Red Road Family Centre and other nurseries in North Glasgow so we will be delighted to look at how we can help them with the children's play area."
A spokeswoman for Police Scotland said: "We have received a report of vandalism having taken place at a nursery in Red Road over the weekend.
"Officers are investigating and we are asking anyone who has any information on who may be responsible to come forward and speak to police."
Information can be given to Police Scotland by dialling the non-emergency number 101 or by calling Crimestoppers anonymously on 0800 555 111.