Climate change is predicted to alter natural flow regimes in glacier-fed streams. These streams are susceptible to rising water temperatures and hydrological variability, due to peak glacier melt and unpredictable precipitation patterns. Although these environmental changes are know to affect stream respiration and food web structures, their impacts on little glacier-fed stream biofilms, the dominant life form in these ecosystems, remain poorly understood. To assess the impact of climate change on glacier-fed streams, benthic biofilms were grown in stream-side flume mesocosms, in the Swiss Alps. Eight treatments were implemented, simulating climate change-driven variation, comprising four flow (natural, intermittent, stochastic and constant), and two thermal (ambient and warming of + 2ºC) regimes. Over a 3-month succession period, we monitored the microbial biomass (cell counts and chlorophyll-a), diversity and composition (16S/18S rRNA, metagenomics), and metabolic diversity (EcoPlates, metatranscriptomics). Stream water warming had little influence on the overall biofilm composition. However, it reduced algal biomass and stimulated heterotrophic metabolism. In contrast, drought events significantly altered biofilms’ microbial community composition, by favoring drought-adapted bacteria and further reducing algal biomass. Drought also triggered a pronounced shift in phototrophs transcriptional activity. Upon rewetting, cyanobacterial activity largely increased, while diatoms metabolism declined, accompanied by their elevated infection by Megaviricetes. Heterotrophic metabolism remained overall unchanged by a short 6-hour drought but was strongly stimulated after a longer 24-hour drought. Notably, a subsequent 24-hour drought did not induce further metabolic changes, suggesting that at later successional stages, glacier-fed stream biofilms can tolerate flow cessation. These findings indicate that while glacier-fed biofilm initially resist short-term drought, prolonged or repeated droughts can substantially reshape their community structure, activity, and function. Climate-driven increases in drought frequency or duration may therefore have lasting impacts for microbial ecosystem functioning in glacier-fed streams.