It is two seasons since the 23-time Turkish champions last won the Super Lig, whilst Kayserispor are well into their seventh consecutive top-flight campaign.
Match preview
On the back of an impressive smash-and-grab victory against Lazio in the Europa League, Galatasaray would have been confident of maintaining their unbeaten start to the season when Alanyaspor travelled to the Turk Telekom Arena on Sunday.
Instead, Daniel Candeias's 87th-minute strike stole the win for Alanyaspor, handing Galatasaray their first defeat of the season in the process.
Back-to-back 2-2 draws against Trabzonspor and Kasimpasa had put the brakes on what had been a perfect start to the season, after Galatasaray cruised to victories in their first two Super Lig fixtures.
An opening-day victory against Giresunspor was followed up by another win over Hatayspor, leaving Fatih Terim's side tipped as early title contenders.
After finishing level on points with Besiktas last season, Galatasaray agonisingly missed out on a 24th title by just one goal, with their Istanbul rivals boasting a +45 goal difference, compared to their tally of +44.
The 2020-21 campaign represented a strong reaction from Galatasaray, who had suffered their worst defence of a Super Lig title since 1970 in the previous campaign, with an underwhelming sixth-placed finish.
Ending what had been at the time a run of two consecutive league championships, questions had begun to surface surrounding the credentials of legendary Galatasaray boss Terim.
In his second spell as manager of the Lions, Terim had previously overseen one of the most successful periods in the club's history, winning four consecutive Turkish league titles between 1996 and 2000.
What's more, Terim was responsible for bringing Galatasaray's only European title to date, triumphing in the 1999-2000 UEFA Cup.
A return to the golden era of years gone by seems unlikely for Galatasaray given the current strength of sides around them in the Super Lig and the Istanbul-based club will want to avoid falling further behind the early season pace setters.
Looking to add even more frustration to Galatasaray's season will be Kayserispor, who themselves have had an indifferent start to the 2021-22 campaign.
Comprehensively beaten by Altay SK in their first match of the season, Kayserispor bounced back with some strong performances either side of the international break, picking up seven points from their next three fixtures.
Unlucky not to have won in their 1-1 draw with Adana Demirspor, the Anatolian Star saw off Istanbul Basaksehir to get their first victory of the campaign, before backing it up with a 2-0 triumph over Kasimpasa.
Hatayspor put an end to their unbeaten streak in Kayserispor's last match, scoring twice after the half-time break to secure a slender 2-1 victory.
If they are to cause an upset and return to winning ways this week, it will be their first victory against Galatasaray since February 2017, a winless run currently at eight Super Lig matches.
Registering a comfortable 3-0 win the last time Galatasaray played at the Kadir Has Stadium in March, the Lions will be confident of getting a result when they travel to Kayseri, as they are unbeaten in their last 12 visits.
A phenomenal run of form that stretches back to August 2008, Kayserispor haven't enjoyed much luck against Galatasaray in recent years and their first objective will be to ensure they finish the match with 11 men on the pitch.
This fixture has seen an astonishing seven red cards handed out in their last six encounters, with all but one of those dismissals given to a Kayserispor player.
Remarkably, Kayserispor saw three players sent off in one match against Galatasaray in August 2019, with an overall total of 14 cards brandished by referee Mustafa Ogretmenoglu.
Whilst they may not have had a man sent off so far this season, do not bet against tempers boiling over once again when these two meet on Wednesday.
Kayserispor Turkish Super Lig form:
Galatasaray Turkish Super Lig form:
Galatasaray form (all competitions):
Team News
Yalcin Kosukavak's Kayserispor side have done well to pick up points early on this season, not least because of their wretched luck with injuries so far.
Mario Gavranovic is yet to make an appearance in the league since his transfer from Dinamo Zagreb in the summer, whilst Ugur Demirok has not featured since late August.
Lionel Carole is another player unlikely to be available for Kayserispor, as the 30-year-old left-back is still recovering from a knock picked up in their win over Kasimpasa.
Similarly, Galatasaray will also be without a number of key players for their trip to Kayserispor, with the most notable being Arda Turan, who has been sat on the sideline since suffering an ankle injury in pre-season.
Sacha Boey is still out with a hamstring injury, whilst Baris Yilmaz will also be absent after the left-winger fractured a bone in his hand.
Omar Elabdellaoui has been out since the new year, when the former Manchester City man was involved in a horrific firework accident.
Kayserispor possible starting lineup:
Lung; Civelek, Kolovetsios, Subasi, Bulut; Bassan, Akdag, Attamah, Thiam; Mensah, Sazdagi
Galatasaray possible starting lineup:
Muslera; Yedlin, Luyindama, Nelsson, van Aanholt; Antalyali, Morutan, Kutlu, Cicaldau, Akturkoglu; Dervisoglu
We say: Kayserispor 1-2 Galatasaray
Boasting an impressive record against Kayserispor in recent years, this fixture could represent the perfect match for Galatasaray to get their campaign back on track.
Travelling to a stadium where they have had some good results of late, it is hard to look past Terim's men for the three points in this one.