On April 30, 2022, Flowers signed with the Indianapolis Colts as an undrafted free agent, following the 2022 NFL draft.[3] He made the Colts' 53 man roster out of training camp. He was the team's primary kick returner, and led the league with 31.1 yards per return.[4] He was named to the PFWA All-Rookie Team.[5]
Flowers entered the 2023 season as a starting cornerback alongside Kenny Moore II. He suffered an Achilles injury in Week 4 and was placed on season-ending injured reserve on October 3, 2023.[6]
The day after a Week 5 game against the Jacksonville Jaguars in which Flowers appeared responsible for allowing an 85-yard touchdown pass to rookie Brian Thomas Jr. and a contributing factor in a four-yard touchdown strike to Brenton Strange in the fourth quarter, Flowers was waived by the Colts.[7]