Climate change is predicted to alter natural flow regimes in glacier-fed streams. These streams are susceptible to increasing water temperatures and hydrological variation, due to peak glacier melt and unpredictable precipitation patterns. Despite the impact of these environmental changes on the overall stream respiration and food web structures, little is known regarding the impacts of thermal and flow changes on glacier-fed stream biofilms, the dominant life form in this ecosystem. Streamside flume mesocosms, growing benthic biofilms, were set up to determine impact of climate change in the European Alps glacier-fed streams. Eight treatments simulated climate change-driven variations and included four flow (natural, intermittent, stochastic and constant), and two thermal (ambient and warming of + 2ºC) regimes. We monitored the biofilms’ microbial biomass (cell counts and chlorophyll-a), diversity and composition (16S, 18S rRNA, metagenomics), and metabolic diversity (EcoPlates, metatranscriptomics) over a 3-month succession period. We found that stream water warming had little influence on glacier-fed stream biofilms’ composition but induced a decrease in algal biomass and stimulated overall heterotrophic metabolism. However, drought events significantly impacted biofilms’ microbial composition, by favouring drought-adapted bacteria and reducing algal biomass. Additionally, drought significantly induced a shift in transcriptional activity of biofilm phototrophs; upon rewetting, the activity of cyanobacteria was largely upregulated, while diatoms metabolism was reduced. Heterotrophic metabolism remained overall unchanged following a short 6-hour drought but was significantly stimulated after a longer 24-hour drought. Interestingly, a subsequent 24-hour drought did not result in any metabolic changes, suggesting that at later successional stages, glacier-fed stream biofilms can withstand flow cessation.