Delpierre, 30, joined Stuttgart from Lille in 2004 and became captain of the club, making 161 Bundesliga appearances.
But, with his contract expiring in June and having fallen out of favour with boss Bruno Labbadia, he has agreed a two-year deal with Hoffenheim.
"Mathieu is an outstanding defender who will give us more experience," Hoffenheim coach Markus Babbel - who played with and coached Delpierre at Stuttgart - said.
"He is a seasoned professional with leadership qualities that will help our young team."
Playing alongside former centre-back Babbel, Delpierre won the 2007 German Cup.
After Babbel was named Stuttgart coach, he appointed Delpierre as club captain, although he resigned the armband in January.