The testament of Romeo Pepoli's Zerra, written by Rolandino de 'Passaggeri on 8 October 1251, shows the presence of the family in the area of via Castiglione at that time.

[2] From the beginning, the Pepoli had established a prominent banking house in Bologna and became among the richest families in Italy at that time.

In August, 1337, Taddeo Pepoli orchestrated an armed occupation of the city and gained support for his election as Lord of Bologna.

While Cardinal Gil de Albornoz forcibly returned the city to the papal orbit in 1360, the Pepoli never regained their former civic power.

A later member of the family, conte Carlo Pepoli, wrote Vincenzo Bellini's libretto for I Puritani and provided the lyrics for Rossini's song "La Danza".