The Old Lady have named previous Azzurri manager the veteran manager as their manager for the remainder of the campaign.
The 66-year-old takes over from Igor Tudor, who was sacked after the Serie A side's defeat by Lazio on Sunday.
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 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.
He secured their spot in 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, with the Azzurri at risk of missing out on a third consecutive World Cup.
Spalletti has also managed 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 placing them seventh in the Serie A standings - 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.
