Oxidative disorders were triggered in the presence of Cd toxicity in early seedling growth of six Medicago truncatula genotypes. Interactions between root growth inhibition, cadmium uptake, as well as the occurrence of oxidative injury suggest differential responses of the genotypes, with susceptible or tolerant accessions. ROS enhancement was observed in situ and H₂O₂ content was measured, that did not seem related to tolerance or susceptibility. Oxidative burst impact on cell membrane integrity was analyzed in agreement with MDA content and glucose exudation, which suggest an active role of this burst in susceptible lines. Transcriptional changes in response to cadmium treatment were analyzed on target genes involved in (1) ROS-scavenging enzymes (superoxide dismutase (SOD; EC1.15.1.1) and peroxidase (PRX; EC 1.11.1.7)), (2) reduced glutathione (γ-Glu-Cys-Gly, GSH) metabolism (glutathione-S-transferase (GST; EC: 2.5.1.18) and glutathione reductase (GR; EC 1.8.1.7)), and (3) metal-chelating metabolism (PCS). The susceptible line shows no response or non-timely gene expression patterns. This research work gave an overview of the deleterious effects and oxidative injury of cadmium stress in Medicago truncatula. Oxidative defense efficiency and gene upregulation should explain relative tolerance in tested genotypes.