During his final seasons in Madrid, Cannavaro's decline began to be evident, especially during the 2008–09 season. Due to his advanced age, he was often seen struggling when faced with pacy opponents such as Lionel Messi and Fernando Torres, leading to Real Madrid conceding any number of goals. On 19 May 2009, it was confirmed Cannavaro would return to Juventus for the 2009–10 season at the conclusion of his contract. On his final match at the Santiago Bernabéu Stadium, he was given a standing ovation by the fans. In April 2013, Cannavaro was named by Marca as a member of the "Best foreign eleven in Real Madrid's history".
Three years after Cannavaro left Juventus, and following the end of his contract with Real Madrid, in the summer of 2009 he decided to return to the club. Cannavaro started the new season very well, forming good defensive partnerships with Nicola Legrottaglie, Martín Cáceres, Zdeněk Grygera, Fabio Grosso and most notably Giorgio Chiellini, in front of goalkeeper Gianluigi Buffon. However, from Autumn onwards, Juventus' form took a turn for the worse. Having been injured for a while in late 2009, Cannavaro struggled with his own form both on his comeback and subsequently, and Juventus were knocked out of the Champions League, finishing third in their group.
In Italy's final 2009 Confederations Cup group match against Brazil, Cannavaro equalled Paolo Maldini's record of being Italy's most capped player, although Italy were defeated 3–0 and were disappointingly eliminated from the tournament in the group stage. On 12 August 2009, in a friendly match against Switzerland, Cannavaro became Italy's most capped player of all time. He won his 127th cap for his country, beating Maldini's former record of 126.
On 8 October 2009, Cannavaro failed a drug test. However, Juventus claimed the drugs were medicine for a severe allergic reaction to a wasp sting, and not performance-enhancing. Because of the urgent nature of the treatment, Cannavaro could not ask for permission to CONI in time, which was done immediately afterwards. Apparently while awaiting the conclusion of formalities involved for CONI with granting this permission, he was subjected to the drug test that eventually gave the positive result. CONI later dropped charges against him.