In an interview with ESPN.com on Friday, the Hall of Fame coach discussed Rose suffering yet another season-ending knee injury after missing all of last season with an ACL tear.
"It's tragic from the standpoint of where he was heading and had already achieved as an MVP," Riley said. "And all of us in this league said this guy is on his way to becoming the best maybe of all time. So he's been short-circuited with two major injuries the last two years. And it will make him stronger. He will come back."
Riley compared Rose's situation to another highly recognized player, one he'd coached during his years with the Los Angeles Lakers.
"I can remember James Worthy, his rookie year when he was about ready to break through and become a superstar, he broke his kneecap on the last day of the regular season," Riley said. "One of the reasons we lost to Philadelphia in the 1983 [NBA Finals] is because James Worthy broke his kneecap. And then the next year, he had very severe tendinitis.
"It wasn't until 1985, after two years of injuries, that he actually got over the injuries, broke through and became 'Big Game James.'"
Worthy went on to reach the Hall of Fame and be named one of the 50 greatest NBA players of all time.
Riley firmly believes Rose can rebound from his injuries and enjoy a similarly illustrious career.
"I think Derrick will overcome this," Riley said. "It's really tragic. It really is -- for him, for the game and for competition and what the game is all about.
"This is something that is difficult for anybody to watch who respects hard work and talent and character. He's a high-character kid. From that standpoint, I think he's going to overcome this thing."
Rose played in 10 games this season before suffering a medial meniscus tear in his right knee. The injury required season-ending surgery Nov. 25.
In the season opener, Rose scored 12 points and had four assists in a 107-95 loss to the Heat.
"Prior to this last injury, you could see he had pretty much come all the way back," Riley said. "He was quick. He was explosive.
"His timing and shooting wasn't there yet. But, to me, this is a temporary setback. And I think he'll be as good as ever."