The Old Lady have named ex- Italy manager the veteran manager to lead the team for the remainder of the campaign.
The experienced coach steps in for Igor Tudor, 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 departed after seven months following a string of eight matches without a victory.
Spalletti led Napoli to the Serie A title in 2022-23 then moving on to lead the Italian national team, which missed out on 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 after a World Cup qualifying defeat by Norway, with the Azzurri at risk of missing out on a third consecutive World Cup.
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 for their 3-1 win against Udinese on Wednesday moving them to seventh position in the league - six points adrift of Napoli at the top after nine rounds.
In the Champions League, they sit 25th in the league phase, having lost once and drawn twice in their opening three matches.
