Both Bisphenol A (BPA) and polystyrene nanoplastics (PSNPs) are routinely found in several consumer products such as packaging materials, flame retardants, and cosmetics. The environment is seriously endangered by nano- and microplastics. In addition to harming aquatic life, nanoplastics (NPs) also bind to other pollutants, facilitating their dispersion in the environment and possibly promoting toxicity induced by these pollutants. The toxic effects of polystyrene nanoplastics (PS-NPs) and BPA were examined in this study, as well as the combined toxic impacts of these substances on the freshwater microalgae Scenedesmus obliquus. In addition, the exopolymeric substances (EPS) secreted by algae will interact with the pollutants modifying their physicochemical behaviour and fate. This work aimed to investigate how algal EPS alters the combined effects of BPA and PSNPs on the microalgae Scenedesmus obliquus. The algae were exposed to binary mixtures of BPA (2.5, 5, and 10 mg/L) and PSNPs (1 mg/L of plain, aminated, and carboxylated PSNPs) with EPS added to the natural freshwater medium. Cell viability, hydroxyl and superoxide radical generation, cell membrane permeability, antioxidant enzyme activity (catalase and superoxide dismutase), and photosynthetic pigment content were among the parameters studied to determine the toxicity. It was observed that for all the binary mixtures, the carboxylated PSNPs were most toxic when compared to the toxicity induced by the other PSNP particles investigated. The maximum damage was observed for the mixture of 10 mg/L of BPA with carboxylated PSNPs with a cell viability of 49%. When compared to the pristine mixtures, the EPS-containing mixtures induced significantly reduced toxic effects. A considerable decrease in reactive oxygen species levels, activity of antioxidant enzymes (SOD and CAT), and cell membrane damage was noted in the EPS-containing mixtures. Reduced concentrations of the reactive oxygen species led to improved photosynthetic pigment content in the cells.