De Bruyne, who was an unused substitute for last weekend's 2-0 win over Sheffield United in the Premier League, is in contention to make his first appearance for the Citizens since tearing his hamstring back in August.
Doku, meanwhile, has returned to the matchday squad for the first time since the beginning of December after recovering from a muscle problem.
However, there is no sign of star striker Erling Haaland, who returned to first-team training earlier this week following a lengthy spell out with a foot injury, but he is not quite ready to return to first-team action and misses out again this afternoon.
A virus has struck the Citizens this week and as a result, Bernardo Silva and Kalvin Phillips - who has been tipped to leave the club in January - are both absent from the matchday squad, but both Matheus Nunes and Scott Carson have recovered in time to feature.
There is also a somewhat surprising appearance of Rodri on the substitutes' bench, as manager Pep Guardiola initially ruled the midfielder out of today's game at a press conference on Friday following the passing of his grandmother.
Guardiola has made a total of five changes to the side that beat Sheffield United last time out, with Rodri, Ederson, Kyle Walker, Nathan Ake and Bernardo all making way for Stefan Ortega, Oscar Bobb, Rico Lewis, Ruben Dias and Sergio Gomez.
A back four of Manuel Akanji, Dias, Ake and Gomez is set to sit behind midfield duo Lewis and Mateo Kovacic, while Bobb, Phil Foden and Jack Grealish all provide support in attack for Julian Alvarez.
As for Huddersfield, Darren Moore has made three changes to the side that lost 4-1 at Leicester City in the Championship on New Year's Day, with the most notable inclusion being Chelsea loanee Alex Matos who is set to make his debut for the Terriers at the expense of David Kasumu.
Brodie Spencer is also handed a start following his recall from a loan at Scottish Premiership side Motherwell, and he takes the place of Yuta Nakayama in defence, while Ben Jackson returns to the first XI after missing the last three games through illness, coming in for Jaheim Headley.
Striker Bojan Radulovic, another new recruit, is among the substitutes, while centre-back Michal Helik, Huddersfield's top scorer so far this season with seven goals, will captain the side in the back three.
Manchester City: Ortega; Akanji, Dias, Gvardiol, Gomez; Lewis, Kovacic; Bobb, Foden, Grealish; Alvarez
Subs: Ederson, Walker, Ake, Doku, Rodrigo, De Bruyne, Nunes, Wright, Hamilton
Huddersfield Town: Nicholls; Spencer, Lees, Helik; Matos, Edmonds-Green, Rudoni, Wiles, Jackson; Thomas, Koroma
Subs: Bellagambi, Ayina, Edwards, Austerfield, Stone, Diarra, Radulović, Hudlin, Iorpenda