The 2016 Indiana State Sycamores football team represented Indiana State University in the 2016 NCAA Division I FCS football season.

They were led by fourth-year head coach Mike Sanford and played their home games at Memorial Stadium.

They were a member of the Missouri Valley Football Conference.

On December 16, head coach Mike Sanford resigned[1] to join the staff at WKU where his son, Mike Sanford Jr., had recently been named the head coach.

Sanford leaves Indiana State with a four year record of 18–30.