The 2021 Nicholls State Colonels football team represented Nicholls State University as a member of the Southland Conference during the 2021 NCAA Division I FCS football season. Led by seventh-year head coach Tim Rebowe, the Colonels compiled an overall record of 6–5 with a mark of 5–3 in conference play, placing third in the Southland. Nicholls State played home games at John L. Guidry Stadium in Thibodaux, Louisiana.