The 28-year-old stated at the show's Comic-Con panel that he would like to see the Time Lord acknowledge the amount of "blood on his hands".
"I think that's why he's so bubbly and cheery, and has to keep going," Smith suggested. "If he didn't, if he stopped, he'd have to contemplate losing all these people. I think there'll be a lot more."
His co-star Karen Gillan added that The Doctor would start facing the consequences of his actions when Doctor Who's sixth series returns on August 27.
"I think in episode ten, we see some of The Doctor's dark side," she said. "Rule number one: The Doctor lies. That's going to be explored."
Smith also shared his hope that the Dream Lord (Toby Jones) from series five would make a reappearance to confront The Doctor with his past.
"He's one of my favourite actors. I'd love to get him back, with a bigger army behind him. If you look at the blood on The Doctor's hands over the ages, there's so much of it."
As well as having to face his inner demons, outgoing executive producer Piers Wenger hinted that The Doctor may be forced to once again battle his oldest enemy - The Daleks.
When asked at the panel if the iconic villains would be back, Wenger replied: "There is only one word that can answer that question, and that's 'spoilers'."
Doctor Who showrunner Steven Moffat claimed in May that there would be no Daleks in series six, while Digital Spy readers have admitted to being bored of them.