Gruebele is married to Nancy Makri, who is also a professor of chemistry and physics at University of Illinois at Urbana-Champaign. They have two children, Alexander and Valerie.
He has a strong interest in cycling, running, swimming and triathlon and has competed in many long-distance events, such as the 2013 Boston Marathon, the 2016 solo Race Across America, the 2019 Badwater Ultramarathon, the 1406 mile DECA 2022 World Championship ultratriathlon, and the Ironman World Championship. He has written two how-to books on ultra-distance cycling and ultratriathlon.