Fijian second-row Leone Nakarawa will make his 50th appearance for the club in front of a capacity crowd of 6,800.
Stuart Hogg and Taqele Naiyaravoro continue at full-back and right wing respectively, while Tommy Seymour comes in for Sean Lamont on the left wing.
Alex Dunbar moves from inside to outside centre, with Peter Horne wearing the number 12 shirt and Mark Bennett not involved this weekend.
Duncan Weir comes in for Finn Russell at fly-half and Mike Blair replaces Grayson Hart at scrum-half.
In the pack Ryan Grant starts in place of Gordon Reid at loose-head, with Malcolm replacing Shalva Mamukashvili at hooker and Tongan prop Sila Puafisi returning in place of Mike Cusack at tight-head.
Nakarawa come in for Tim Swinson and partners captain Jonny Gray in the engine room.
In the back-row Josh Strauss replaces Rob Harley at blind-side, Simone Favaro comes in for Chris Fusaro at open-side and after his match-winning try against Benetton Treviso, Adam Ashe continues at Number 8.
Mamukashvili, Swinson, Rob Harley, Finn Russell and Sean Lamont are all named on the bench after starting last Friday's match, while Jerry Yanuyanutawa and Zander Fagerson come into the matchday squad.
Glasgow Warriors head coach Gregor Townsend said: "Anytime you play Leinster is exciting. They've been the best team in our league over the last five or six years and they've got real quality.
"Leinster come into the game off the back of a very good win last weekend against Ulster and they are one of the teams in the top half of the table who will be looking to get a string of results to move them up into the play-off positions.
"James (Malcolm) has worked really hard in training and made notable contributions when he came on against Cardiff Blues and Benetton Treviso, so he deserves the opportunity to start tomorrow and we're looking forward to seeing him play."
Glasgow Warriors team to play Leinster, GUINNESS PRO12, Scotstoun Stadium, Saturday 5 December (kick-off 3pm) - live on Sky Sports 1:
15. Stuart Hogg
14. Taqele Naiyaravoro
13. Alex Dunbar
12. Peter Horne
11. Tommy Seymour
10. Duncan Weir
9. Mike Blair
1. Ryan Grant
2. James Malcolm
3. Sila Puafisi
4. Leone Nakarawa
5. Jonny Gray (Captain)
6. Josh Strauss
7. Simone Favaro
8. Adam Ashe
Replacements
16. Shalva Mamukashvili
17. Jerry Yanuyanutawa
18. Zander Fagerson
19. Tim Swinson
20. Rob Harley
21. Ali Price
22. Finn Russell
23. Sean Lamont
Not available due to injury: Fraser Brown (foot), Glenn Bryce (ankle), Kevin Bryce (shoulder), Mike Cusack (ribs), Tyrone Holmes (foot), Rory Hughes (shoulder), Kieran Low (concussion), Pat MacArthur (jaw), Peter Murchie (elbow), Henry Pyrgos (wrist), D'arcy Rae (back), Gordon Reid (neck), Fergus Scott (shoulder), Richie Vernon (shoulder) and Ryan Wilson (calf).
