The widespread use of pharmaceuticals and personal care products (PPCPs) has raised serious concerns regarding their potential ecotoxicological effects. We examined the photosynthetic toxicity of four non-steroidal anti-inflammatory drugs (NSAIDs), i.e. ibuprofen (rac-IBU and S-(+)-IBU), aspirin (ASA) and ketoprofen (KEP) on the green alga Scenedesmus obliquus. Our results showed that NSAIDs exerted inhibitory effects on algal growth; the IC of S-(+)-IBU, rac-IBU, ASA, and KEP was 123.29, 107.91, 103.05, and 4.03 mg/L, respectively. KEP was the most toxic, ASA was slightly more toxic than rac-IBU, and S-(+)-IBU was the least toxic. NSAIDs adversely affected the cellular ultrastructure, as evident from plasmolysis, chloroplast deformation and disintegration. NSAID treatments decreased the chlorophyll and carotenoid content, and chlorophyll fluorescence parameters such as minimum fluorescence yield (F), maximum fluorescence yield (F), maximum photochemical quantum yield (F/F), PSII (photosystem II) effective quantum yield [Y(II)], photosynthetic electron transfer rate (ETR), and the photochemical quenching (qP), were also adversely affected. Algal photosynthetic and respiratory rates decreased following NSAID treatments, and the expression of genes involved in photosynthetic electron transport (psaA, psaB, psbB, psbD, and rbcL) was down-regulated. Furthermore, the functioning of the photosynthetic electron transport chain from PSI (photosystem I) to PSII, carbon assimilation, and photorespiration were affected. Our results suggest that NSAIDs can exert considerable toxic effects on the photosynthetic system of S. obliquus. These results provide a basis for evaluating the environmental safety of NSAIDs.