Influential Bayern captain Lahm is set to miss at least three months of action after fracturing his ankle during a training session on Tuesday.
The news is a further blow to Bayern coach Pep Guardiola, who is already without centre-back Holger Badstuber (thigh), full-back David Alaba and midfield trio Thiago Alcantara, Javi Martinez and Bastian Schweinsteiger (all knee) - although the latter has recently returned to training.
Despite the latest disappointment, Gisdol is adamant that champions Bayern will not be weakened when the teams return to action after the international break in Saturday's clash at the Allianz Arena.
"The injury to Philipp Lahm is of course tragic, but these things happen in football," he said.
"[But] you can list every player in their squad and they would all play a major role in every big club in Europe.
"Munich have the best and widest squad in the league. No matter who runs out at the Allianz Arena, for Hoffenheim it is an incredibly tough game."
Gisdol's assessment is a fair one considering Bayern's only competitive defeat this season came in the DFL Supercup to Borussia Dortmund and they top the Bundesliga with 27 points from 11 matches, four clear of second-placed Wolfsburg.
But Bayern will need no reminding of the quality that Hoffenheim possess after the corresponding fixture last season finished 3-3 in March, with the visitors overturning a 3-1 deficit.
And Gisdol is relishing the challenge of trying to orchestrate Hoffenheim's first Bundesliga win over Bayern.
"We know that our team can be good, but we also have respect for Bayern," he added.
"[We will] take on the challenge and look forward to the game. 12 times Hoffenheim and Bayern met in the Bundesliga, four times we fought to a draw, eight times it was a defeat.
"But the two most recent meetings are encouraging."
To pull off an unlikely shock, Hoffenheim must bounce back from two straight league defeats, including the thrilling 4-3 reverse to Cologne last time out.
Gisdol must make do without defensive midfielder Eugen Polanski (dead leg), but Kim Jin-su could come into contention after a thigh injury.
Bayern's injury concerns could have been worse as goalkeeper Manuel Neuer (knee), Jerome Boateng (calf) and Thomas Muller (knock) all sustained injuries while on international duty with Germany.
However, the trio should all be available for selection.