The contamination of aquatic environments by heavy metals can have detrimental effects on fish, impacting their growth and overall health, including the regulation of antioxidant genes. An investigation was carried out to assess the distribution and habitat of Gymnocypris eckloni in the Yellow River basin. Simultaneously, heavy metal concentrations in its habitat and in selected locations within the upper Yellow River were measured. In an effort to explore the potential roles of specific genes in antioxidant responses, G. eckloni was exposed to low concentrations of copper (Cu2+) and lead (Pb2+) for varying durations (12, 24, and 48 hours). The mRNA levels of GeCu/Zn-SOD, GeMn-SOD, GeHsp90, and GeMT were quantified in the gills, kidneys, and liver through qRT-PCR. The findings suggest that the habitat of G. eckloni is generally safe; however, occasional exceedances of safety standards could pose a potential threat to its growth. Importantly, the expression of GeCu/Zn-SOD, GeMn-SOD, GeHsp90, and GeMT exhibited responses to the low concentrations of copper-induced and lead-induced stress. Notably, GeCu/Zn-SOD, GeMn-SOD, and GeMT demonstrated heightened sensitivity to lead compared to copper. Furthermore, the expression of these genes displayed tissue-specific responses under identical metal stress conditions. These results indicate that GeCu/Zn-SOD, GeMn-SOD, GeHsp90, and GeMT genes have the potential to serve as early, sensitive biomarkers for the detection of metal toxicity induced by Cu2+ and Pb2+. This study also provides valuable insights into the functioning of antioxidant genes under oxidative stress in fish.