McAnuff, 39, has made over 150 appearances for Orient and captained the Club to the National League title in the 2018/19 season.
Commenting on the appointment, Chairman Nigel Travis said: “Jobi is a natural leader and someone we feel has got what it takes to make a top class manager.
“As a Club we feel that the play-offs are still within reach for this season and we have made that clear to Jobi, who understands and agrees with us that it should remain our focus and target.
His appointment gives us a degree of continuity but also a fresh approach for the final third of the season.”
McAnuff, whose completion of his UEFA A License has been delayed due to Covid-19, will work with the Club’s existing coaching staff of Danny Senda, Dean Brill and Matt Harrold.