The Old Lady have chosen ex- Italy manager Spalletti to lead the team for the rest of the term.
The 66-year-old steps in for the Croatian manager, who was sacked following the loss to Lazio last weekend.
The former boss came on board in March as Thiago Motta's replacement but left after seven months following a string of eight matches without a victory.
Spalletti guided Napoli to the Serie A crown in 2022-23 prior to assuming the Italy role, who had failed to qualify for the 2022 World Cup with Mancini at the helm.
He helped them qualify for Euro 2024 where they were knocked out in the last 16 by Switzerland.
Nonetheless, Italy dismissed Spalletti in June following a loss to Norway in World Cup qualifying, as Italy faced the possibility of not making a third World Cup in a row.
Spalletti's managerial career includes Inter Milan, Roma, and Udinese in Serie A and won the Russian Premier League twice with Zenit St Petersburg.
Massimo Brambilla served as interim manager for Juventus during the 3-1 victory over Udinese on Wednesday which left them seventh in Serie A - six points adrift of Napoli at the top after nine rounds.
Their Champions League campaign sees them in 25th place in the group stage, having lost once and drawn twice in their opening three matches.