The Dutchman is yet to oversee a win as Red Devils boss, having lost to Swansea and drawn with Sunderland, but will hope to record a maiden victory over lower-league opposition
The Dutchman has not made the early impact a fine pre-season suggested he might have at Old Trafford, a 2-1 home defeat against Swansea City preceding a lacklustre 1-1 draw at Sunderland.
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And Van Gaal will be targeting an improvement in United's passing, which he bemoaned following the draw at Sunderland.
He said: "We were dominating but you need creative passing in the last third and that was also not so good.
"We do not want to be dominating without creating chances. Creating chances and making goals is the purpose of a game. We must improve the passing."
Adding to Van Gaal's concerns is a growing injury list. New signings Ander Herrera (ankle) and Luke Shaw (hamstring) are both set to be sidelined over the coming weeks, while United are also without Michael Carrick (ankle) and Jesse Lingard (knee).
It is a similar story in defence, where Chris Smalling was withdrawn against Sunderland due to a groin injury, meaning United were forced to deploy two youngsters - Tyler Blackett and Michael Keane - alongside Phil Jones in a back three.
Van Gaal said: "It is unusual to have four injuries in midfield. Every club that has that has a problem.
"That is why I played [Adnan] Januzaj in midfield [as a substitute versus Sunderland]. When you have a lot of injuries like now then you always need players."
However, there may be good news on that front with the potential availability of new signing Marcos Rojo, who missed out against Sunderland having not received a work permit.
United reached the semi-final stage of the competition last season, but were beaten by Sunday's opponents Sunderland.
MK Dons have made an encouraging start to their League One campaign, winning two and drawing one of their first four matches and they will be eager to claim a major scalp in order to progress to the third round.
Defender Lee Hodson (ankle) is set to miss out once again for the home side and it remains to be seen if goalkeeper David Martin (hip) is available to return.