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Objective: The objective of the study was to identify Nrf2 activators from differently treated Morinda citrifolia L. fruit juices and their cytotoxicity. Materials and Methods: Noni fruit juices were prepared by different treatments: unripe (T1), ripe (T2), purchased (T3), and Noni juices fermented with Lactobacillus plantarum (T4). These extracts were tested for Nrf2 activation and nuclear factor kappa B (NF?κB) inhibition activities. These active extracts were further studied for their nuclear Nrf2 translocation and induction of HO?1 protein expression. Finally, the active extracts were purified using open column chromatography and RP-high pressure liquid chromatography (HPLC) techniques through bioassay?guided separation. Moreover, all Noni juice samples were tested for cytotoxicity using mammalian cell?based methylthiazoltetrazolium (MTT) assay. Results: Only purchased (T3) and ripe Noni fruit juices fermented with LP at 22℃ (T4–22) showed strongest Nrf2 activation and NF?κB inhibitory activity. Further, these two extracts enhanced the nuclear accumulation of Nrf2 after 2 h and also promoted Nrf2 and HO?1 nuclear translocation. Induction of HO?1 gene expression of Hep G2/ARE cells treated with T3 confirmed that it is a potent inducer of the Nrf2 target gene HO?1. Bioassay?guided separation resulted in subfractions with high Nrf2 activity. The strongest Nrf2 active subfraction led to the identification of scopoletin as an Nrf2 activator. Moreover, none of the tested samples showed any cytotoxicity for the MTT assay. Conclusions: The presence of potential Nrf2 activators in the Noni fruit juices that were nontoxic in our MTT assay could mitigate the production of harmful reactive species in the biological systems, and thereby, could helpful in alleviating and prevention of chronic diseases.