Chlorella vulgaris (C. vulgaris) and Scenedesmus obliquus (S. obliquus) were compared to remove toxicity under conditions of sludge extract cultivation for 30 days. The toxicity of sludge extract, the growth characteristics, photosynthetic pigment, superoxide dismutase (SOD) enzyme and catalase (CAT) enzyme activities of the two microalgae were studied by contrast. The results showed that small molecular organic matter (<500 Da) was more easily utilized by microalgae. The toxicity in the toxic group of C. vulgaris and S. obliquus on the 30th day decreased to 56.8 ± 1.2% and 60.7 ± 2.8%, respectively. In the toxic group, the maximal SOD enzyme activity of C. vulgaris and S. obliquus were 2.02 U/mg proteins and 8.21 U/mg proteins, respectively, demonstrating that toxicity caused more oxidative damage to S. obliquus than to C. vulgaris. Proteomics analysis revealed that C. vulgaris mainly regulates energy synthesis and distribution primarily through sugar metabolism, and biomass synthesis primarily through carbon metabolism, whereas S. obliquus mainly regulates energy synthesis and distribution primarily through sugar metabolism and oxidative phosphorylation, resulting in sludge toxicity stress regulation. [Display omitted] • C. vulgaris ' ability to adapt to toxicity was stronger than S. obliquus. • Both C. vulgaris and S. obliquus decreased the toxicity to less than 50%. • Toxicity caused more oxidative damage to S. obliquus than to C. vulgaris. • C. vulgaris regulates energy and biomass through sugar and carbon metabolism. • S. obliquus regulates energy through sugar metabolism and oxidative phosphorylation. [ABSTRACT FROM AUTHOR]