Boron nanoparticles have numerous medical, industrial, and environmental applications as potential nanomaterials. Given the inevitable release of these particles in aquatic environments, they can combine with other pollutants like pharmaceuticals. Therefore, it is necessary to investigate their combined detrimental effects on freshwater biota. This study examined the joint impacts of Boron nitride nanoparticles (BNNPs) and Diclofenac (DCF) on freshwater microalgae Scenedesmus obliquus. Three different concentrations of BNNPs (0.1, 1, and 10 mg L−1) were mixed with 1 mg L−1 of DCF and were treated with algal cells, and biochemical analyses were performed. A concentration-dependent decrease in algal cell viability was observed after a 72-h interaction period with BNNPs and their binary combinations. The maximum toxic effects were observed for the highest combination of BNNPs + DCF, i.e., 10 mg L−1 BNNPs + 1 mg L−1 DCF. Similarly, an increase in the oxidative stress parameters and antioxidant enzyme activity was observed, which correlated directly to the decline in cell viability. The algal cells also showed reduced photosynthetic efficiency and electron transfer rate upon interaction with BNNPs. The results of this research emphasize the importance of considering the negative consequences of emerging pollutants and their combinations with other pollutants, BNNPs, and DCF as part of a thorough evaluation of ecotoxicity in freshwater algal species.