The Ligue 1 side recorded a surprise 1-0 win over Juve in the first leg of their last-16 tie in February before the season was suspended due to the coronavirus pandemic.
Depay, 26, missed that clash after rupturing his anterior cruciate ligament (ACL) in December, but is reportedly ready to return to training in June.
Sylvinho, who was at the helm of Lyon for 11 games last year, believes the attacker's return could give the club the upper-hand.
"Lyon had a good result at home, but there is also the comeback and playing at Juventus is very difficult," the former Barcelona and Arsenal left-back told Sky Sport on Sunday.
"I don't know if Depay will be able to return, but if he succeeds, it could make a real difference. He is strong physically and technically and he has character.
"I like him so much. If he is able then Lyon will have an advantage."
Depay has scored 14 goals and provided two assists in 18 games this season and his return would be a boost for Lyon, with the Champions League to potentially be completed in August.