The 36-year-old former France international damaged the medial collateral ligament in his left knee and has decided to call it quits. Mathieu’s contract at the Portuguese club would have expired this month.
Mathieu played in the French Ligue 1 with Sochaux and Toulouse before securing a transfer to Valencia in the summer of 2009.
After five seasons at the Mestalla stadium, Mathieu joined Barcelona, where in three seasons, he won two La Liga titles, one UEFA Champions League, three Copa del Reys, one FIFA Club World Cup, one UEFA Super Cup and one Supercopa de Espana.
Portuguese newspaper Record quoted a statement from Mathieu, in which he said: "I thought I would end my career in another way, but it is part of football. I wanted to finish on the pitch so badly, but destiny decided otherwise.
"Anyway, I spent 19 years living my life with intense passion, with ups and downs, joy and crying, victories and defeats and incredible trophies."
Manchester United midfielder Bruno Fernandes, who played alongside Mathieu for two-and-a-half seasons at Sporting, was one of the first people to pay tribute to the Frenchman.
Fernandes posted on Instagram: "I had news that left me sad and crestfallen.
"I learned that the best centre-back I ever had as a team-mate was injured and decided to end a career full of titles and unforgettable moments."
"I had two and a half years with you, two and a half years of apprenticeship, two and a half years of eternal bets in training to see who scored the most free-kicks, two and a half years to see magic come from the feet of a centre-back, yes from a centre-back."
"Thanks for the tears in the final of the Taca de Portugal that showed me what it is like to love the game and how all victories are as important as the first."