Sybrina Fulton, who became an activist against gun violence following her son’s death, will enter the race to join the 13-member board of Miami-Dade County commissioners.
Ms Fulton said she would continue working to end gun violence, the Miami Herald reports.
She will challenge Miami Gardens mayor Oliver Gilbert for the seat, which is up for grabs in 2020 because of term limits.
Trayvon’s parents head a foundation and have been recognised for their work on gun reform and social justice.
Trayvon was unarmed when he was shot dead by neighbourhood watch volunteer George Zimmerman in 2012.
Mr Zimmerman had followed the 17-year-old and told a 911 dispatcher he looked like a “real suspicious guy”.
He was later acquitted on the grounds of self-defence.
Mr Zimmerman was also arrested on suspicion of domestic violence in 2015, but was not charged after the alleged victim withdrew her claims.
He sparked outrage in 2016 when he auctioned the gun he claimed was used to kill Trayvon for $250,000 (£184,000).
He has since been banned from dating app Tinder after using a fake name, and blocked on Bumble too.