In 2008, he joined his former River Plate manager Ramón Díaz at Argentine club San Lorenzo. However, after Díaz left the club, D'Alesandro opted to move to Brazil to play for Internacional. Playing for the former Copa Libertadores champions, he described as a "step forward" in his career.
On 13 December 2008 it was reported on ESPN Deportes that the Los Angeles Galaxy had made a $10 million offer to Internacional for D'Alesandro but was declined. Their vice president Fernando Carvalho was quoted; "The offer came from the Los Angeles Galaxy of the United States. I didn't even want to listen to the details. The offer was for more money than we paid for D'Alessandro, who arrived here for five million euro, but we want to keep the Argentinian." D'Alessandro has become one of Internacional's most idolized players of all time along the likes of Falcão, Valdomiro, and Fernandão. In 2008, he was part of Inter's Sulamericana Championship. In 2009 Internacional finished in second place in both the Brasileirão and Copa do Brasil. In 2010, D'Alessandro led Internacional to their second Libertadores Championship, and was elected the best player in South America for that year; in the 2010 FIFA Club World Cup, he also helped Internacional to a third-place finish, and was awarded the Bronze Ball as the tournament's third best player. In 2011 D'Alessadro had personally an even better year, but Internacional only managed to win the State Gaucho Championship. 2012 was a bad year for both Internacional and D'Alessandro. Furthermore, rumours of him leaving to play in China caused a major distraction; after long drawn out drama he stayed but soon was injured. In 2013 his game improved again, and while Inter only won the State Championship, he was praised as the only positive factor of the team that year. 2014 started well; D'Alessandro continued to play well and led Inter to their 4th straight Gaucho Championship.