His style runs to bright colours and detail — especially buttons, often made of gold or gems, which became his trademark — and earned him comparisons to Versace. He dressed Queen Sofía of Spain, Lauren Bacall, Susan Sarandon, Halle Berry, Cher and Sharon Stone, and in 2000 designed four chasubles for Pope John Paul II.
Over the years his business spread across couture, larger sizes, textiles, footwear, accessories and perfume, with collaborator and partner Attilio Vaccari. He launched Gai Mattiolo Wedding in 2011; his most recent collection was released in 2020.