The Oscar-winner walked out on her husband in March after a tattooed model went public with claims of an 11-month affair with James.
Bullock recently announced she has filed for divorce, and is intending to raise the couple's newly-adopted son, Louis, by herself.
Shatner, who is friends with the former couple, admits the publicity surrounding the scandal has taken its toll on James, who checked into rehab shortly after the news broke to seek treatment for personal issues.
Shatner tells The Insider, "My heart goes out to Sandra, who I know and love. My heart goes out to (Jesse). I was at their wedding. I know he loved her. That marriage, that wedding was just beautiful.
"Jesse's being tormented like a matador with a bull. The paparazzi have nothing to lose so they are constantly waving the red flags. He's in a terrible emotional state. His whole life has been turned upside down. He doesn't know what he's doing right now."
And Shatner still hopes his friends will be able to mend their broken relationship.
He adds, "To me it's not beyond the realm of possibility that they get back together. (Jesse) made a mistake."