The couple announced their separation in December, 14 months after they were married at a Hindu ceremony in Jaipur, India.
The 66-year-old actress, who became close friends with Brand after they starred in last year's Arthur remake, said that she was upset to hear about his split with Perry and suggested that there is still potential for a reunion.
"It's very hard to keep things going," she reminded In Touch. "Maybe they'll come back together again later on in life!"
The Oscar winner went on to speculate that the couple's hectic schedules likely contributed to their break-up, noting: "They're both very, very successful."
Recent reports have suggested that Perry is keen to reconcile with Brand, even choosing to continue wearing her wedding ring.
The Get Him to the Greek star commented on his divorce for the first time yesterday (January 15), saying that he is starting to question what is "newsworthy" following tabloid rumors about their split.
> Helen Mirren: 'I'm jealous of Katy Perry'
Watch Katy Perry in the video for 'The One That Got Away' below: