The Serie A powerhouse have named former Italian national team manager the veteran manager to lead the team for the rest of the term.
Spalletti takes over from Igor Tudor, who was dismissed after the Serie A side's defeat by Lazio recently.
Tudor had joined the club in March to replace Thiago Motta but departed after seven months at the end of an eight-match winless run.
Spalletti led Napoli to the Serie A title in 2022-23 prior to assuming the Italy role, which missed out on the 2022 World Cup with Mancini at the helm.
Under his guidance, they made it to Euro 2024 where they were knocked out in the last 16 by Switzerland.
However, Spalletti was sacked by Italy in June after a World Cup qualifying defeat by Norway, 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 moving them to seventh position in the league - six points adrift of Napoli at the top after nine rounds.
They are 25th in the league phase of the Champions League, with one loss and two draws in their first three games.
