Abstract: Bisphenol A (BPA) and its substitutes, acting as environmental endocrine disruptors, are ubiquitously present in environmental matrices and human biological samples. The associated health risks from exposure to these compounds are a subject of considerable concern. This article systematically reviews the mechanisms by which BPA and its substitutes disrupt the gut microbiota-host metabolic axis to induce metabolic disorders. Research has revealed that these compounds impair short-chain fatty acid (SCFA) production, interfere with bile acid metabolic reprogramming, and disrupt tryptophan-kynurenine balance, triggering intestinal barrier damage, systemic inflammation, and multi-organ toxicity. Gut microbiota serve as a critical therapeutic target, with its reduced diversity directly associated with an imbalance in pro-inflammatory/anti-inflammatory bacteria ratios, which in turn mediates trans-organ toxicities via metabolites affecting the gut-liver axis, gut-brain axis, and other pathways. Notably, some substitutes like bisphenol AF (BPAF) exhibit heightened bioaccumulation and metabolic interference potential compared to BPA. Existing evidence suggests that targeted modulation of the gut microbiota (such as probiotic intervention and dietary fiber supplementation) demonstrates promise in restoring SCFA balance and repairing the bile acid-FXR/TGR5 signaling axis, thereby mitigating toxicity. Future research may integrate multi-omics technologies with cross-species models to establish microbiota sensitivity-based risk assessment frameworks for substitutes, thereby providing a new strategy for stratified environmental health risk management. This study has laid the foundation for understanding the mechanism of enterotoxic effects of bisphenols and the development of microbiota-based intervention measures.