The Old Lady have appointed former Italian national team head coach the veteran manager to take the helm for the rest of the term.
Spalletti steps in for the Croatian manager, who was let go after the Serie A side's defeat by Lazio recently.
The former boss came on board in March filling the shoes of Thiago Motta but left after seven months at the end of an eight-match winless run.
Under Spalletti, Napoli clinched the Serie A championship in 2022-23 then moving on to lead the Italian national team, who had failed to qualify for 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 following a loss to Norway in World Cup qualifying, putting Italy in danger of missing a third straight World Cup.
Spalletti's managerial career includes Inter Milan, Roma, and Udinese in Serie A and secured two Russian Premier League titles 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 behind leaders Napoli after nine games.
Their Champions League campaign sees them in 25th place in the group stage, after recording one defeat and two ties in the initial three fixtures.
