Dembele sustained the injury in Saturday's 3-2 Premier League win at Wolves, having to be replaced after only seven minutes at Molineux, and Spurs fear he will not return until the new year.
Dembele will also be missing for upcoming London derbies against Arsenal and Chelsea in the Premier League, as well as December's Carabao Cup clash with the Gunners, but manager Mauricio Pochettino could soon have Victor Wanyama available.
TEAM NEWS: @mousadembele (ankle) - scans have confirmed ligament damage to right ankle and is unlikely to be available until the New Year. pic.twitter.com/twfAUTMoKh — Tottenham Hotspur (@SpursOfficial) November 8, 2018
The Kenya midfielder has been restricted to three substitute appearances in the Premier League this season, but Spurs confirmed he has returned to training following a knee injury.
Eric Dier is also in contention to feature in Saturday's Premier League game away to Crystal Palace, but defenders Jan Vertonghen (hamstring) and Danny Rose (groin) are both still out.