To understand the adverse outcome in response to bisphenol A and its analogs bisphenol F and S (BPA, BPF, and BPS), we examined acute toxicity, life parameter, and defensome in the marine rotifer Brachionus koreanus. Among the bisphenol analogs, BPA showed the highest acute toxicity and then BPF and BPS, accordingly in the view of descending magnitude of toxicity. In life parameters including life span and reproduction, BPA, BPF, and BPS were found to cause adverse effect. Both intracellular ROS level and GST activity were significantly increased (P < 0.05) in response to each dosage of bisphenol analogs exposures. In response to bisphenol analogs, defensomes of phase I, II, and III detoxification mechanism demonstrated inverse relationship between the lipophilicity of bisphenol analogs and the expression patterns of defensomes. BPA and BPF were found to have significant modulation (P < 0.05) in the expression of cytochrome P450 (CYP) and GST genes. In phase III, BPS with comparatively lower lipophilicity demonstrated highly diversified expressional pattern, suggesting that BPS is likely caused less toxicity compared to BPA and BPF. In this study, via phase I, II, and III detoxification mechanism, bisphenol A and its analogs F and S demonstrated specific detoxification mechanism in rotifer.