The Old Lady have named ex- Italian national team head coach the veteran manager to take the helm for the remainder of the campaign.
The 66-year-old takes over from the Croatian manager, who was dismissed post the Lazio setback recently.
The former boss came on board in March as Thiago Motta's replacement but exited following a seven-month stint 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 during Roberto Mancini's tenure.
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, 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 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.
In the Champions League, they sit 25th in the league phase, after recording one defeat and two ties in the initial three fixtures.
