The 36-year-old came through the youth system at Blackburn, before moving onto Chelsea, Newcastle and then Fulham.
Duff won two Premier League titles, an FA Cup and League Cup during his career, in addition to helping the Cottagers to the 2010 Europa League final.
The winger won 100 caps for Ireland, representing them at the 2002 World Cup and Euro 2012, and returned home to join Shamrock Rovers in July.
Duff penned an 18-month contract after leaving Australian outfit Melbourne City, but has brought his time with the Dublin club to a premature end.
"After much deliberation, I have today decided to bring my professional football career to an end," he said in a statement released by Shamrock.
"My heart wants me to continue playing but my body has finally won the battle and told me to stop.
"I've lived every young boy's dream and I know I am a very lucky man.
"I would like to thank everyone who has helped me along the journey from schoolboy football in Dublin and moving to England as a teenager right up to today.
"I am extremely proud to have won 100 caps for my country - it was always my greatest pleasure to represent Ireland and I have many magical memories from my international career.
"While I have finished playing, I am progressing with my coaching badges and will stay involved in the game for many years to come.
"I am grateful to Pat Fenlon and Shamrock Rovers F.C. for giving me the opportunity to finish my career back home - they have some exciting plans for the club for the future and I wish them well. I had hoped to play for one more year but it was not to be.
"Thank you to all the many fans for your support over the years.
"I would like to especially thank my wife Elaine, my children, my parents Gerard and Mary and my family for being, and continuing to be, my biggest supporters."