Diabetic retinopathy (DR) is a progressive neurovascular disorder due to damage to retinal blood vessels. Beta-carotene acts as retinal chromophores and initiates photo-transduction and epithelial maintenance. Beta-carotene (BC) is present in palm oil mill effluent, and it is called palm oil mill effluent-derived beta-carotene (PBC). The present study is designed to evaluate the effect of PBC in streptozotocin-induced DR in zebrafish by measuring the oxidative stress, inflammation, and polyol pathway markers. The five groups of healthy Danio rerio were used in this study. The diabetes retinopathy was instigated by intraperitoneal administration of streptozotocin (STZ) followed by intravitreal administration of STZ on the 7th day. The exposure of PBC (50 and 100 mg/L) and dexamethasone (DEX) was administered for 21 continuous days. The DR-associated visual behaviours i.e., optomotor response (OMR) and startle response (SR) were appraised on 0, 7, 14, and 21st days. The biochemical changes i.e., plasma glucose & homocysteine (HCY); retinal tissue lipid peroxidation, reduced glutathione (GSH), tumor necrosis factor-alpha (TNF-α), superoxide dismutase (SOD) and total protein levels were estimated. The lens was used for the evaluation of polyol pathway markers i.e., sorbitol dehydrogenase (SDH) and aldose reductase (AR) activity. The PBC potentially attenuated the DR with the regulation of biochemical abnormalities which is similar to DEX treated group. Hence, PBC can be used for the management of DR due to its anti-hyperglycemia, antioxidant, anti-inflammatory, and polyol pathway regulatory actions.