Host Kaley Cuoco was joined by her castmates in a pre-recorded segment that aired at the start of the awards show.
The cast - including Cuoco and her co-stars Johnny Galecki, Jim Parsons, Simon Helberg, Kunal Nayyar, Mayim Bialik and Melissa Rauch - sat around the series' living room set discussing the People's Choice Awards.
"They're the best. They're the only ones actually chosen by the people," Cuoco said, in character as Penny.
"Who's hosting this year?" Rauch asked.
"Some blond bimbo from a sitcom. If it's not Neil Patrick Harris, who cares?" Cuoco responded.
The actress then proceeded to receive a phone call from her agent telling her that she had been hired as a seat filler.
"She'll be great at that. She's been practicing on this couch for years," Parsons quipped as Sheldon.
The pre-recorded segment then transitioned into the live show, where Cuoco was sitting next to Betty White. The 89-year-old Hot in Cleveland star told the actress that she was wanted for the hosting gig.
"Does it pay more?" Cuoco asked her.
She then took to the stage, where she pointed out Harris in the audience.
"Neil, why are you wearing a microphone?" she asked.
"I always wear this," he answered.
Cuoco pointed to Harris's two beautiful companions, asking: "Who are those people sitting next to you?"
"Who, these two?" he responded. "They're my parents."
"Really, those super hot chicks in their bedazzled outfits are your parents?" she answered, as he responded: "They've had a lot of work done."
Cuoco then approached Harris and pulled at his suit, asking why it was looking "weird" before tearing off the shirt.
"A tearaway tuxedo. Neil, you have a problem," she declared.
"You're right, I'm addicted," he answered before bursting into song. Cuoco then cut him off and had him escorted out of the theatre.
More from the People's Choice Awards 2012:
> Betty White gets standing ovation at People's Choice Awards 2012
> Nathan Fillion wins 'Favourite TV Drama Actor' at 2012 PCAs
> Nina Dobrev wins 'Favourite TV Drama Actress' at People's Choice Awards
> People's Choice Awards 2012: The winners
Browse a gallery of images from the ceremony below: