In this study, curcumin derivatives salicylidenecurcumin (CD1) and benzalidenecurcumin (CD2)] were prepared, and their biological activity was compared in in vitro selenite-induced cataract model. The antioxidant activity was studied using DPPH radical scavenging assay. Knoevenagel condensates of curcumin exhibited higher DPPH radical scavenging activity compared with curcumin. The anticataractogenic potential of curcumin derivatives was analyzed using lens organ culture method. The activity of antioxidant enzymes and calcium homeostasis was reversed to near normal levels following treatment in organ cultured rat lenses. These results indicated that curcumin and its derivatives-CD1 and CD2-are beneficial against selenite-induced cataract in vitro. Of these, CD1 is having higher bioactive potential compared with curcumin and CD2. Blindness is a common condition globally, affecting approximately 45 million people, and more than a third of blindness is caused by cataract (1). Approximately 25% of the population with age over 65 and about 50% over 80 have serious loss of vision because of cataract (2). Cataract is a protein aggregation disease affecting vision in humans. At present, the most effective treatment for cataract is surgical extirpation of the opaque lens, but it is expensive and not free from risk factors (3). It is widely accepted that oxidative stress is a significant factor in the genesis of cataract (4). Oxidative stress may result from an imbalance between the production of reactive oxygen species (ROS) and the cellular antioxidant defense mechanisms.Oxidative metabolism is clearly important in maintaining the lens in a transparent state. The lens is metabolically active and requires nourishment to maintain its growth and transparency. Like other organs, lens has a well-designed defense system against oxidation. It uses both enzymatic and non-enzymatic defense system to neutralize free radicals that are clearly involved in the pathophysiological changes in the eye (5). Selenite-overdose cataract is an extremely rapid and convenient model to study experimental cataract. Major events of selenite cataract are loss of calcium homeostasis, reactive oxygen species generation, and decreased water soluble proteins (6).Medicinal plants often contain highly active pharmacological compounds. Many of these compounds, isolated from a part or whole of the medicinal herbs, act as pharmaceutical drugs having therapeutic potential against cataract (7-11). Curcumin is well known for its flavoring and medical properties and shown to exhibit antioxidant, antiinflammatory, antimicrobial, and anticarcinogenic activities. The medicinal properties of curcumin are attributed to its radical scavenger activity and are shown to scavenge free radicals such as hydroxyl radicals, superoxide radicals, singlet oxygen, peroxyl radicals, and peroxynitrite (12). Thus, curcumin can reduce the oxidative stress in tissues and hence a potential candidate as an anticataract agent. In spite of its efficacy and safety, curcumin has not yet b...