Smith became the third player in as many matches this term to be sent off for the Dons when he was given his marching orders against Bournemouth on Tuesday night.
The former England international departed after just 19 minutes with his team 1-0 behind on the south coast, but Daniel Powell's second league goal of the season rescued a 1-1 draw for Karl Robinson's side.
Smith begins a three-match suspension while midfielder Stephen Gleeson completes a three-match ban and defender Antony Kay will serve the second part of his three-game absence.
Luke Chadwick, who came off the bench against Bournemouth, could replace Smith in midfield at the County Ground.
On the injury front, the versatile Shaun Williams (ankle) resumed training on Thursday but the game could be too soon for him while defender Mathias Kouo-Doumbe (knee) is still unavailable.
Swindon boss Paolo Di Canio may name an unchanged side.
The Robins thrashed fellow league new boys Crawley 3-0 in midweek and the Italian may opt for the same starting XI.
Former skipper Paul Caddis is certain to miss out after his ongoing feud with his manager came to an end after the defender was told he could leave the club.
Midfielder Gary Roberts is yet to make an appearance this season since joining in the summer. He continues to struggle with a calf injury and will be assessed ahead of kick-off.
Fellow midfielder Alan Navarro and striker Paul Benson are both pushing for a recall but may have to settle for a place on the bench again.