Mispelaere was previously the creative director at designer Diane von Furstenberg's company, reported Women's Wear Daily.
Mispelaere's first collection for Roberto Cavalli will be the fashion giant's autumn/winter 2014 designs, which will be unveiled at Milan Fashion Week in February 2014.
The French fashion designer left his post at New York-based DVF in September 2012 after two-and-a-half years as the brand's lead creative chief.
His departure was announced just days after showcasing his spring/summer 2013 line-up at New York Fashion Week.
At the time, Mispelaere said he was 'eager to take on my next challenge', while Diane von Furstenberg praised him for adding 'enormous value' to her fashion house during his time with the company.