The midfielder, who has helped the club rise from the third tier of English football to an eighth place finish in the Premier League, has not been offered a new deal at St Mary's
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The Premier League club confirmed on Saturday that midfielder Guly will depart St Mary's Stadium along with strikers Lee Barnard and Jonathan Forte as the trio are out of contract and have not been offered fresh terms.
Brazil-born Guly made over 100 appearances for Southampton after joining from Cesena in 2010, initially on loan before his move became permanent. The 32-year-old played an integral part in the club's rise from League One to the top flight and weighed in with 23 goals.
"Southampton Football Club would like to thank those players leaving for their efforts whilst representing the club, and wishes them all the very best for the future," read a club statement.
While Guly, Barnard and Fonte prepare to continue their careers elsewhere, Cody Cropper, Lloyd Isgrove, Sam McQueen, Omar Rowe and Jake Sinclair have been offered new deals to stay at Southampton.
McQueen, Sinclair, Rowe and Isgrove have all made first-team appearances for the club this season, with the latter also spending time out on loan at Peterborough United.