The 32-year-old actor had the "worst night ever" when he returned to find rodents had laid faeces all over the floor, while one large critter was relaxing in his bed.
During an appearance on 'The Billy Bush Show', he revealed: "I go upstairs and there was a huge rat in my bed. And like, poop and faeces all over my bed. It was just the worst night ever."
The star - who plays teacher Will Schuester in 'Glee' - wasn't going to let the rats get away with taking over his house, however, and a chase quickly developed.
He explained: "I tried to catch the rat and he darted away. And I kind of cornered him in this thing. I thought he was dead on my bed.
"So I put a bunch of plastic bags on my hand, and I went to grab him and he just darted off. He was on the windowsill, kind of just eyeing me. We were playing cat and mouse - or Matt and rat, I guess!"
Matt eventually managed to capture the rat, but although he threw him in a "far away trashcan" and went to bed, his rodent problems were far from over.
He added: "I get up, run over and turn the light on, and this big guy is on my nightstand and he jumps on my bed. And he's looking at me like, 'What are you doing on my bed?' He's looking at me like I'm the a**hole."
After this ordeal, Matt admitted temporary defeat and checked into a hotel, and now wants to put his house up for sale.