The midfielder has been sidelined since picking up a knee ligament injury while on international duty with the Republic of Ireland last October.
The Toffees manager told the club's website: "Darron Gibson is fully fit and he looks a refreshed, regenerated player. He's been training in an impressive, impressive way and I would expect him to be involved with the squad.
"Arouna [Kone] and Bryan [Oviedo] are both doing well in their recoveries. Darron Gibson without a doubt will be ready [for Tranmere]. The other two, it would be an unnecessary risk at this stage.
"They are three important players who know Everton inside out, and now they're getting into a position where they want to have a big role on the pitch and they want to help the team. That's really positive because they're three players who we've missed for a long, long time."
The match is due to take place at Prenton Park tomorrow evening.