The former Prison Break star will appear in the Fox drama's eighth run as House's latest patient, according to TV Line.
"He plays a real altruist," revealed House creator David Shore. "And there's some question as to whether that's his symptom or not."
Miller is best known for playing Michael Scofield on Fox's Prison Break from 2005 to 2009, and has also appeared in episodes of Law & Order: SVU and Buffy the Vampire Slayer.
Earlier this year, the actor signed up to appear in ABC drama pilot Identity, but the project was not picked up to series.
Other guest stars confirmed for the new season of House include The Lincoln Laywer actor Michael Paré and former child star Jaleel White.
Breaking In's Odette Annable and Knocked Up's Charlyne Yi will also join the show as series regulars.
House returns to Fox on Monday, October 3. Miller's episode will air later in the month.
> House Jesse Spencer: 'Lisa Edelstein exit was difficult'
Watch a promo for the eighth season of House below: