The presenter told the crowd to get over the Kristen Stewart and Robert Pattinson cheating scandal.
The comedian presented the ceremony in Los Angeles, California and decided to ''address the elephant in the room'' by discussing her affair with Rupert Sanders.
The 32-year-old told the audience at the Staples Center: ''Everybody's mad at Kristen Stewart for making a mistake. She allegedly messed around with the director of 'Snow White and the Huntsman'.
''If she did, so what? It's over. Move on. Look on the bride side, they're now a part of the seven dwarfs. You've got sleepy, grumpy, adultery, cheating.''
The actress was caught cheating on her 'Twilight' co-star and real-life boyfriend of three years in mid-July.
Kevin continued: ''The point that I'm making is this, if you made a mistake . . . so what!''
The star claimed that he would be making mistakes of his own hosting the show and went on to mention numerous mistakes the network had made in its history.
The 2012 MTV Video Music Awards will air on Friday (07.09.12) at 9pm on MTV UK, Sky 126 and Virgin 311.
Full list of winners:
Best Video With A Message - Demi Lovato, 'Skyscraper'
Most Share-Worthy Video - One Direction, 'What Makes You Beautiful'
Best Electronic Dance Music Video - Calvin Harris, 'Feel So Close'
Best Pop Video - One Direction, 'What Makes You Beautiful'
Best Male Video - Chris Brown, 'Turn Up The Music'
Best Hip-Hop Video - Drake, 'HYFR'
Best Female Video - Nicki Minaj, 'Starships'
Best Rock Video - Coldplay, 'Paradise'
Best New Artist - One Direction, 'What Makes You Beautiful'
Video of the Year - Rihanna, 'We Found Love'