The actor, 55, stars as Odysseus in Sir Christopher Nolan's adaptation of Homer's epic as he makes the journey home to Ithaca after the Trojan War.
Speaking on Radio Andy with host Andy Cohen, Damon told how the cast were also left with cuts on their feet due to the sandals they wore for the ancient setting.
He said: "A lot of us are middle-aged people and what we got was back pain.
"Oh my God, running through Troy, like, you know, it's all stone.
"You're in these sandals and they're very real. Our feet were all scuffed up.
"But more than the scratches and cuts on your feet, it was the back pain for us.
"It was a heavy Advil movie in those weeks when we were doing all that action stuff."
Damon underwent a physical transformation for the film, dropping his weight to 76 kilograms and growing a beard for a year before production.
He told People magazine: "It was more about just getting really, really physically fit.
"Which just really involves changing your diet. I stopped eating gluten, among other things.
"You have to just be very, very intentional about everything you put in your body."
The cast also includes John Leguizamo, 66; Jon Bernthal, 49; Samantha Morton, 49; and Anne Hathaway, 43.
The Odyssey set a record for Sir Christopher's biggest box office debut and has received acclaim from critics, with some hailing it as his best film to date.
Younger co-star Tom Holland said he felt "intimidated" when he met the acclaimed director for the first time.
The 30-year-old, who will also return to the role of Spider-Man in Brand New Day later this month, said he was "pinching himself" when he was asked to play Telemachus.
"I mean, obviously the first word out of your mouth is 'yes'," Holland said.
"I was really intimidated to meet him, but he's a very disarming person, he's really kind, he's really personable, and he was really open about the ambition of what he wanted to try and do.
"And I love film, I love making movies, I love watching movies, and I was just excited as a fan of cinema to hear what he was planning on doing, and then to get the chance to be in it was just… I'm still to this day kind of pinching myself.
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