After five wins, 22 podiums and nine pole positions during his time in the 250cc World Championship, de Puniet joined the MotoGP class with the Kawasaki team in 2006, qualifying fourth at his home race in Le Mans and placing tenth in Portugal for his best finish his debut year. The French rider celebrated his first MotoGP podium in 2007 at Motegi, placing 10th in the final standings despite failing to finish seven of the 18 races due to frequent crashes. In 2008 de Puniet signed with the Honda LCR Team, where he remained for three seasons, running fifth in the Championship in 2010 until breaking his leg at the Sachsenring round, demoting him to ninth by the end of the season. 2011 saw de Puniet move to the Italian based Pramac Racing Team aboard a Ducati alongside Loris Capirossi, though multiple DNFs saw De Puniet finish 16th in the standings. A return to the Aspar Team in 2012 saw De Puniet work with the team to develop its Aprilia powered CRT motorcycle, fighting for top CRT spot until the final round. He remained with the team for 2013 and took another host of point-scoring finishes. In 2014 he took on the Suzuka 8H, took second and pole, and he appeared back in the Grand Prix paddock with Team Suzuki Ecstar in the final round of the season - debuting the new MotoGP™ project from the Hamamatsu factory. He rode for Voltcom Crescent Suzuki in WorldSBK in 2015 and took consistent points when he finished as the team struggled with DNFs. He then rode in the FIM Endurance World Championship and has become a regular Suzuka 8H contender. The veteran Frenchman returns to the Grand Prix paddock as a competitor in 2019 in MotoE™, riding with the LCR E-Team - an outfit he competed with previously in MotoGP™.