It will be Medard's final international outing since February of last year when he tore cruciate ligaments in his right knee against Scotland.
Trinh-Duc and Mathieu Bastareaud drop to the replacements bench with Benjamin Fall missing out on a place in the 23-man squad.
The Michalak-Morgan Parra combination is the third different half-back partnership France will have fielded in this year's Championship.
Parra, who will make his 50th Test appearance on Saturday, was joined by Trinh-Duc for the 23-13 defeat to England last time out.
Les Bleus opened the Six Nations with Maxime Machenaud and Michalak in the number 9 and 10 shirts respectively, Machenaud is on the bench for the trip to Dublin.
The French management have kept faith with the starting pack from the English game, with hooker Benjamin Kayser flanked by his Clermont Auvergne club-mate Thomas Domingo and the experienced Nicolas Mas in the front row.
The two-times capped Christophe Samson links up again with Yoann Maestri in the second row, with captain Thierry Dusautoir leading an all-Toulouse back row.
There are two new additions to the bench in hooker Guilhem Guraido and lock Sebastien Vahaamahina, with Dimitri Szarzewski and Jocelino Suta the players to make way.
Hoping his side can get back to winning ways, Philippe Saint-André said: "The French team's role is to win and win well but in our situation, we'd take a 3-0 victory.
"You've got to make your own luck. We didn't face up to the situation in the first three matches (against Italy, Wales and England).
"We've got to score when we're playing well, concede fewer points when we're not (and) be better defensively.
"Against England, when we scored, we weren't aggressive enough in the first line of defence. We missed a lot of first tackles. We've worked on that to be tighter against Ireland. We've got to learn to win matches again."
FRANCE Team & Replacements (v Ireland, 2013 RBS 6 Nations Championship, Aviva Stadium, Saturday, March 9, kick-off 5pm):
Club/International Caps -
15 - Yoann Huget (Toulouse/15)
14 - Vincent Clerc (Toulouse/65)
13 - Florian Fritz (Toulouse/28)
12 - Wesley Fofana (Clermont Auvergne/13)
11 - Maxime Medard (Toulouse/30)
10 - Frederic Michalak (Toulon/62)
9 - Morgan Parra (Clermont Auvergne/49)
1 - Thomas Domingo (Clermont Auvergne/22)
2 - Benjamin Kayser (Clermont Auvergne/15)
3 - Nicolas Mas (Perpignan/59)
4 - Christophe Samson (Castres Olympique/2)
5 - Yoann Maestri (Toulouse/12)
6 - Yannick Nyanga (Toulouse/29)
7 - Thierry Dusautoir (Toulouse/57) (capt)
8 - Louis Picamoles (Toulouse/34)
16 - Guilhem Guirado (Perpignan/15)
17 - Vincent Debaty (Clermont Auvergne/14)
18 - Luc Ducalcon (Racing Metro 92/13)
19 - Sebastien Vahaamahina (Perpignan/1)
20 - Antonie Claassen (Castres Olympique/1)
21 - Maxime Machenaud (Racing Metro 92/7)
22 - Francois Trinh-Duc (Montpellier/47)
23 - Mathieu Bastareaud (Toulon/12)