Mark DeSantis may refer to:

• Mark DeSantis (businessman) (born 1959), American entrepreneur and political pundit
• Mark DeSantis (ice hockey) (born 1972), Canadian ice hockey defenceman and coach
• Marko DeSantis (born 1972), American lead guitarist for rock band Sugarcult
• Mark DeSantis, professor of finance, see Gunduz Caginalp
• Mark DeSantis, outside linebacker with the 1976, 1977, and 1978 Michigan Wolverines football teams

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