We present here a comprehensive study depicting the differences in biochemical responses to increasing CdCl₂ concentrations (0.1, 0.25, 0.5 and 1.5 mM) in the two indica rice varieties, IR-29 (salt-sensitive) and Nonabokra (salt-tolerant), in order to contribute to our understanding of genotypic variation of cadmium tolerance. The oxidative damages in both the varieties enhanced with the increase in CdCl₂ concentrations, the susceptibility of IR-29 being more pronounced than Nonabokra. The detrimental effects in IR-29 were reflected in greater chlorophyll loss, higher H₂O₂and malondialdehyde content even at lower concentrations and drastically higher lipoxygenase activity, protein oxidation and putrescine accumulation, especially at higher CdCl₂ levels. The antioxidants like anthocyanin and carotenoids, antioxidative enzymes like guaiacol peroxidase (GPX) and ascorbate peroxidase (APX), osmolytes like proline, reducing sugars, spermidine and spermine, increased in both the varieties with CdCl₂ levels. While anthocyanin, reducing sugars and spermine showed greater increment in IR-29, the GPX/APX activity was more enhanced in Nonabokra; the increase in carotenoids, proline and spermidine being similar in both the varieties. However, reverse trends were noted for cysteine level and CAT activity; IR-29 showed marked decrease in cysteine content and CAT activity with increased cadmium exposure, whereas in Nonabokra, both the parameters increased, particularly at higher cadmium levels. Thus, the detoxification mechanism in the moresusceptible IR-29 was probably rendered by anthocyanin, reducing sugars and spermine in particular, as well as by GPX/APX, rather than cysteine and CAT, which showed cadmium sensitivity. Thus, the CdCl₂ stress-dependent comparative biochemical analyses displayed major differences in the two rice varieties in terms of tolerance to Cd toxicity. Our data provides evidence that Nonabokra, which is a well-known variety tolerant to sodium chloride toxicity, also shows promising tolerance to cadmium toxicity, and hints at their possible utilization in Cd remediation.