Antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs) have a wide range of bioactivities and are released into the ecosystem in large amounts. Heretofore, little information is available regarding their potential risk to the phytoplankton assemblage. Different alpha, taxonomic, and beta diversity measures were investigated and linked to the spatial variation of nine drugs. Distance-based redundancy analysis (dbRDA) indicated that pharmaceutical pollution had adverse effects on both phytoplankton diversity and taxonomic structure leading to the existence of congeneric taxa. However, different phytoplankton groups respond differently to different pharmaceuticals and Cyanoprokaryotes was suggested as the most sensitive group. According to the EC₅₀ value and the detected concentration for each drug, a hazard index (Hq) was calculated for each polluted site to investigate environmental risk analysis. Increasing Hq values exhibited negative effects on phytoplankton diversity. Phytoplankton community was characterized by high beta diversity values, which suggested that microalgae were able to disperse and select suitable environmental conditions. High beta diversity values were driven by species difference rather than species replacement due to the disappearance of most sensitive taxa from highly polluted sites. Additionally, microalgae were classified into different morpho-functional groups (FGs), and principal component analysis (PCA) indicated that different FGs had different responses to pharmaceutical pollution. A laboratory toxicity experiment was also conducted to identify the negative effects of short-term exposure to low doses of paracetamol and ciprofloxacin.