De Puniet began his international career in the 125cc class and was crowned French 125cc champion in 1998. He moved to the 250cc World Championship in 2001, and by 2002 had earned two podium finishes, sufficient to secure a factory Aprilia seat for 2003. That year he took his first win at the Catalan Grand Prix and ultimately finished fourth overall with three victories. In 2004 he was third in the championship with a single additional win, spending 2005 aboard an Aprilia run by former world champion Jorge Martínez and the Aspar Team.
De Puniet made his MotoGP debut in 2006 with the Kawasaki factory team, remaining there for 2007. During that year he recorded a career-best qualifying of front row at the Catalan Grand Prix and finished a career-best fifth position. At Motegi in the wet he qualified fourth and finished second.
LCR Honda signed de Puniet for 2008 and 2009. A fractured ankle sustained in a mid-season testing crash in 2009 disrupted his form. Despite links to the Tech 3 Yamaha squad, he remained with LCR for 2010. That season produced some of his best MotoGP form: he recorded consecutive front-row starts at Silverstone and Assen and was running fifth in the championship before breaking his leg in a crash at the Sachsenring. He missed the Laguna Seca round before returning at Brno.
For 2011 de Puniet moved to Pramac Racing on a satellite Ducati. After a difficult year he joined the Power Electronics Aspar team for 2012, operating under the Claiming Rules Team regulations aboard an Aprilia RSV4-based machine known as the ART.
De Puniet did not compete full-time in 2014, instead focusing on development and testing duties for Suzuki's 2015 MotoGP project. He received a wildcard start at the season finale in Valencia, from which he retired.
In 2015 de Puniet contested the Superbike World Championship with limited success. He subsequently moved to the MotoE World Cup, competing aboard an Energica Ego Corsa electric motorcycle. In 2021 he competed in the FIM Endurance World Championship with Moto Ain.
De Puniet is a member of the Champions for Peace club, a group of more than ninety elite athletes created by Peace and Sport, an international organisation operating under the High Patronage of Prince Albert II of Monaco.
Randy de Puniet was a tenacious and technically capable rider who achieved genuine success in the 250cc class and showed consistent MotoGP pace at LCR Honda before injuries disrupted his best seasons. His five 250cc victories and his front-running form at Silverstone and Assen in 2010 represent the high points of a career that kept him active in motorcycle racing across multiple series into the 2020s.