Based on garden cress significantly used for phytoremediation, the antioxidant system included antioxidant-phenolic compounds and antioxidant-enzymes of 6-day-garden cress sprouts (GCS) were assessed as potential bio-indicators for cadmium (Cd) and lead (Pb) contamination. Total phenolic and flavonoid contents of GCS germinated under Cd and Pb treatments (25–150 mg kg−1) gradually increased with increasing concentration of metals and peaked by 2.0, 2.6, and 2.5, 2.3 folds at 150 mg kg−1, respectively. By using DPPH, ABTS, and PMC antioxidant assays, the total antioxidant activity of phenolic compounds of GCS increased 6.1, 13.0, and 5.8-fold for Cd and 5.9, 14.6, and 8.2-fold for Pb at 150 mg kg−1, respectively. The antioxidant enzymes of GCS (POD, CAT, GR, and GST) were significantly activated in response to Cd and Pb stress, and two new electrophoretic POD bands were detected. GCS was absorbed 19.0% and 21.3% of Cd and Pb at 150 mg metal kg−1, respectively. In conclusion, the approaches of the antioxidant defense system of GSC could potentially be used as bio-indicator for monitoring Cd and Pb contamination in a short time of germination process.