Ann Kirton, who runs St Francis Animal Rescue, in Stanhope Road, South Shields, says her charity has been hit four times in recent months.
In the latest incident, the raiders ransacked a store of donations made to the charity shop - which was opened 25 years ago - leaving volunteers to pick up the pieces.
Ann, 72, said: “All we’re trying to do is help animals. We’re all volunteers. No one gets a salary and we all dedicate our time to raise money so we can help.
“They rummage through all the bags of clothes and donations and left a horrendous. The girls in the shop then have to spend time cleaning it all up.
“I could cry now thinking about it. It really upsets me.”
She said: “At the same time, you have no idea how many lovely people I have met through this.
“I’ve been doing this for nearly 40 years and the kindness of lovely people who have supported us or come to us in the past far outweighs the scumbags who would do this.
“They’re not gaining anything from it.”
“At some stage we have probably helped the family and friends of the people who have done this.”
She added: “It just goes on and on. If you look back in the Gazette 30 years ago there will be a picture of me talking about the same thing.
“We’re just trying to help. We couldn’t do what we do without the support of the public and we’re so grateful for all their donations over the years.”
The raid happened on April 8
The charity is currently running a scheme to help low income families get their cat neutered and microchipped for £20.
The charity has also paid for operations when a beloved pet has fallen ill or been involved in an accident.
A Northumbria Police spokesman said: “We received a report from the St Francis Animal Rescue shop on Stanhope Road about anti-social behaviour outside the premises.
“They reported that people had been entering their rear yard and going through piles of old clothes and charity bags that had been left outside the rear of the shop. “Staff at the shop had complained that the anti-social behaviour was causing a mess in the rear yard.
“Although no criminal offences are believed to have taken place, officers have carried out patrols in the area to deter those responsible.”