Tony Pulis brought ex-Dutch international Peter Hoekstra back into the side but that was the only highlight of the fixture against his former club.
Both teams started slowly with neither side having any clear attacking play, the only glimmer of a chance came when the Potters' John Eustace hit a tricky ball from 25 yards but the saw it fly just over Jason Brown's bar.
Five minutes later the Gills' David Perpetuini watched Danny Spiller head wide from his left wing cross.
He tried again after 26 minutes but this time struck gold when Mark Saunders met his cross from just inside the area and floated the ball into the top right corner, leaving Neil Cutler in the Stoke goal helpless.
Stoke thought they had found themselves a small measure of composure after the break, only for Gillingham to mount another offensive seven minutes into the second half.
Yet again, Cutler was left completely stranded when Marlon King scorched a blinding drive from 30 yards into the top left hand corner.
The Potters' problems got worse when Marcus Hall lost his temper and received his second yellow of the night with 25 minutes to play.
Stoke did improve slightly in the closing stages mainly due to the introduction of Kris Commons. The talented youngster nearly capitalized in an 83rd minute mix-up in the Gills' defence, but Brown got down well and managed to parry his effort round the post.
Victorious manager Andy Hessenthaler commented: "Our performance has carried on from the weekend and we've kept a clean sheet so I am well pleased.
"Even though it's a cup game, it's still a confidence booster and now we get the chance to go into the third round against the big boys."
Stoke: Cutler, Russell, Williams, Hoekstra, Marcus Hall, Clarke, Eustace, Goodfellow, Asaba, Noel-Williams, Neal. Subs: de Goey, Akinbiyi, Iwelumo, Henry, Commons.
Gillingham: Jason Brown, Nosworthy, Cox, Hope, Hills, Saunders, Smith, Spiller, Perpetuini, King, Sidibe. Subs: Bossu, Tommy Johnson, Leon Johnson, Rose, Crofts.
Referee: M Ryan (Lancashire).