Pharmaceutical products (PPs) and nanoplastics (NPs) are two prevalent emerging contaminants that have garnered extensive environmental focus. The present study aimed to investigate both pristine and combined toxicity of PPs (metronidazole, diclofenac, and ibuprofen) and polystyrene NPs (with NH2 and COOH surface functionalization). Our findings suggest that Chlorella sp. experienced only a slight growth impediment when exposed to pristine PPs (1 mg/L). In contrast, PSNPs (1 mg/L) resulted in substantial growth inhibition. However, the combination of PPs and PSNPs showed a reduction in toxic effects when compared to pristine PSNPs. Additionally, independent action modeling revealed that the combination of PPs and PSNPs resulted in an antagonistic mode of interaction. Zeta potential analysis revealed the colloidal instability of PSNPs in the presence of PPs. This could have facilitated the aggregation and rapid settlement of PSNPs, consequently lessening their direct contact with the algal cells. Furthermore, ROS production significantly decreased in the combinations compared to the pristine PSNPs. This decrease in the ROS production subsequently led to a reduction in antioxidant activity and an enhancement in photosynthetic efficiency in the cells. These findings provide valuable insights into combined toxicity effects of PPs and PSNPs on primary producers like microalgae.