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.

The Southland Conference released their preseason poll in July 2021.

[1] In addition, eleven Colonels were chosen to the Preseason All-Southland Team.