Heavy metals and plastics pollutions in the environment are becoming more common due to their extensive usage in our everyday lives and improper waste management. Interaction between heavy metals with plastics has been shown to have negative effects to the ecosystem. The aim of this study was to investigate the influence of polyethylene (PE) microplastic (MP) and nanoplastic (NP) on the combined toxicity of copper (Cu) and cadmium (Cd) in microalgae. The effects of PEMP and NP on the toxicity of Cu and Cd were assessed based on the algal physiological responses such as photosynthetic pigment contents and oxidative stress response. Our results showed that after 10 days of exposure, Cu and Cd caused more growth inhibition to Raphidocelis subcapitata (CuIC50=32.32 mg/L, Cd IC50=23.25 mg/L) compared to Chlorella sp. TJ6-5 (CuIC50=34.77 mg/L, Cd IC50=36.45 mg/L). Combinations of Cu and Cd at various IC concentrations (IC10, IC25, IC50, IC90) displayed synergistic effects and caused higher observed toxicity to both algal species compared to the expected level of toxicity. Although PE MP and NP did not cause significant growth inhibition to both algae species at concentrations up to 2 g/L. However, presence of PE MP and NP did enhance the growth inhibition effect of Cu and Cd (at IC50) on both algal strains with higher lipid peroxidation and reactive oxygen species (ROS) production. In addition, our results showed the combined exposure to mixture of PE MP and NP and Cu and Cd can compromise the cellular antioxidant defence capacity, potentially leading to increased susceptibility to oxidative damage and cellular death. In conclusion, the presence of PE MP/NP enhance the toxicity of Cu and Cd to freshwater microalgae particularly in R. subcapitata and Chlorella sp., with species-specific responses and varying degrees of synergistic effects.