During his time at Roma, he was able to help the squad to a fourth-place finish during the 1997–98 season, and managed to subsequently reach the quarter-finals of the 1998–99 UEFA Cup and the 1997–98 Coppa Italia.

[3][4] At the beginning of the 1999–2000 Serie A season, Di Biagio transferred to Inter Milan, and became a regular first team member due to his continued high standard of performance.

Although he was unable to win a title during his time with the club, he did manage to reach the semi-finals of the 2001–02 UEFA Cup with Inter, losing out to eventual Champions Feyenoord.

[3][4] Di Biagio signed for Ascoli in November 2006, but the bid was not considered to be valid by the federation, since the player was not released for free by Brescia before the 30 June deadline.

The bid was therefore postponed until January 2007, and in the meantime Di Biagio went on training with Ascoli, and played from November to December with Promozione club Polisportiva La Storta from Rome, coached by his friend and former Dundee and Lazio footballer Alessandro Romano.

[14] Di Biagio was a regular member of the national side during the late 1990s and early 2000s,[15] and was capped 31 times for Italy between 1998 and 2002, scoring two goals.

[18][19] In the round of 16 match against Norway, Di Biagio set up Vieri's match-winning goal, and helped Italy to keep a clean sheet.

[16] Under Giovanni Trapattoni, Di Biagio was also a member of Italy's 2002 World Cup squad that was eliminated by co-hosts South Korea in the Round of 16 on a golden goal.

Furthermore, he was known for his ability to either set the tempo of his team's build-up plays with short exchanges, or start counter-attacks with long balls after winning back possession.

A hardworking player, Di Biagio was gifted with power, stamina, and tactical intelligence, as well as an acute defensive awareness and positional sense.

He combined these attributes with a surprising technical ability, and was also capable of functioning creatively as a deep-lying playmaker in midfield, due to his ball control, vision, and passing range.

[30][38] Indeed, his central holding midfield role under Zdeněk Zeman in the manager's 4–3–3 system has also been likened to that of a metodista ("centre-half," in Italian football jargon), due to Di Biago's ability to dictate play in midfield, launch quick attacks, or assist his team defensively, as well as to maintain his position and thus allowing his teams to maintain a high defensive line with little space between the attack and the defence.

[39] Despite his more defensive playing role in midfield, Di Biagio also possessed a powerful shot from distance, and was a dangerous free kick and penalty kick taker, which also enabled him to contribute offensively[4] Additionally, he excelled in the air, in spite of his relatively short stature, due to his elevation, physical strength, and heading accuracy, which made him a goal threat in the opposing box during set-pieces.

[42] He eventually helped the U-21 side to qualify for the upcoming 2015 Under-21 European Championship in the Czech Republic, as Italy defeated Slovakia once again in the play-offs.