‘Cara Cara’ is a red orange (Citrus sinensis(L.) Osbeck) variety originally from Venezuela characterized by a significantly higher and diversified carotenoid content including higher-concentration lycopene,all-E-β-carotene, phytoene, and other carotenoids when compared with the carotenoid profile of its isogenic blond counterpart ‘Bahia’, also known as Washington navel. The exceptionally high carotenoid content of ‘Cara Cara’ is of special interest due to its neuroprotective potential. Here, we used the nematodeCaenorhabditis elegansto analyze the antioxidant effect and the protection againstβ-amyloid-induced toxicity of pasteurized orange juice (POJ) obtained from ‘Cara Cara’ and compare to that from ‘Bahia’. POJ treatment reduced the endogenous ROS levels and increased the worm’s survival rate under normal and oxidative stress conditions. POJ treatment also upregulated the expression of antioxidant (gcs-1,gst-4, andsod-3) and chaperonin (hsp-16.2) genes. Remarkably, ROS reduction, gene expression activation, oxidative stress resistance, and longevity extension were significantly increased in the animals treated with ‘Cara Cara’ orange juice compared to animals treated with ‘Bahia’ orange juice. Furthermore, the body paralysis induced byβ-amyloid peptide was delayed by both POJs but the mean paralysis time for the worms treated with ‘Cara Cara’ orange juice was significantly higher compared to ‘Bahia’ orange juice. Our mechanistic studies indicated that POJ-reduced ROS levels are primarily a result of the direct scavenging action of natural compounds available in the orange juice. Moreover, POJ-inducedgst-4::GFPexpression and –increased stress resistance was dependent of the SKN-1/Nrf2 transcription factor. Finally, the transcription factors SKN-1, DAF-16, and HSF-1 were required for the POJ-mediated protective effect against Aβtoxicity. Collectively, these results suggest that orange juice from ‘Cara Cara’ induced a stronger response against oxidative stress andβ-amyloid toxicity compared to orange juice from ‘Bahia’ possibly due to its higher carotenoid content.