Isochrysis galbana, a crucial primary producer and food source in aquatic ecosystems, faces increasing challenges from climate change and emerging contaminants like antibiotics. This study investigates the combined effects of sudden temperature increase (representing marine heatwaves) and rapid salinity change (representing extreme precipitation events) on the toxicity of tetracycline (TC) and oxytetracycline (OTC) to I. galbana. Short-term experiments reveal heightened antibiotic toxicity at 31 °C or salinities of 18 PSU, surpassing algal tolerance limits. Long-term tests show decreased inhibition of algal growth on day 9, indicating algal adaptation to the environment. Analyses of photosynthesis II efficiency, pigment content, and macromolecular composition support this, suggesting adaptation mechanism activation. While algae acclimate to the environment during long-term antibiotic exposure, extreme weather conditions may compromise this adaptation. These findings have implications for managing antibiotics in aquatic environments under climate change.