On 26 October 2016, Marchisio returned to the pitch after six months on the sidelines in a 4–1 home win over Sampdoria. He scored his first goal since his injury in the 3–1 win away at Sevilla during the Champions League group stage. The season saw Marchisio reach two milestones. On 15 April 2017, he made his 250th Serie A appearance for Juventus in a 2–0 away win over Pescara. On 21 May 2017, he started in the last home fixture of the season against Crotone, which Juventus won 3–0 to seal a historic sixth consecutive "Scudetto", which made Marchisio one of only six players to have been in the squad for all six successful seasons. On 3 June, Marchisio came on as a substitute in his second Champions League Final in three years, but Juventus were defeated 4–1 by defending champions Real Madrid.