Having signed with Heart in October, the 33-year-old defensive midfielder had to wait over three months to get on the pitch, coming off the bench in his side's 1-0 defeat at Western Sydney Wanderers.
But having injured his calf in Saturday's game, Grella has decided to retire after playing just 211 minutes of top-flight football in the past two years.
"After 17 years of professional football my body has told me it's enough," Grella said in a statement released by Melbourne Heart.
"I need to thank (Heart head coach) John Aloisi and the club for giving me a final chance to continue as a professional.
"I felt the club's culture was the perfect place for me to be and it's frustrating I won't have the opportunity to contribute to it and to John's first steps as a coach."
Grella joined Heart from Blackburn, having barely played in his final two seasons with Rovers before heading to the A-League.
He also enjoyed spells with Parma and Torino during his career and won 46 international caps, including appearances at the 2006 and 2010 World Cups.