Santana has been on the seven-day concussion list since he took a foul tip off the mask on May 25 against the White Sox.
"I'm feeling a lot better," Santana said on Sunday. "I really want to play."
Indians manager Manny Acta indicated that Santana had passed the latest neurological test required by Major League Baseball on Saturday and doesn't expect him to need another exam. Santana caught a bullpen session before Sunday's game against the Twins and took batting practice in the indoor cage.
"He's doing well," Acta said. "We're very optimistic that we're going to have him for that Detroit series."
The three-game set with the Tigers begins Tuesday.