P-phenylenediamines (PPDs) and their quinone derivatives (PPDQs), emerging pollutants widespread in urban environments, exhibit biotoxicological risks. Epidemiological studies suggest their adverse impacts on intestinal health, yet the underlying mechanisms remain unclear. This study aimed to investigate the potential mechanisms of enterotoxicity induced by 13 PPDs and PPDQs using network toxicology and molecular docking approaches. Through the SuperPred, STITCH, GeneCards, and OMIM databases, 182 potential targets associated with PPD- and PPDQ-induced enterotoxicity were identified. Thirty hub targets, including SRC, EGFR, CASP3, and others, were prioritized using STRING and Cytoscape tools. GO and KEGG enrichment analyses via the DAVID and FUMA databases revealed significant enrichment of core enterotoxicity-related targets in the MAPK signaling pathway and the calcium signaling pathway. Molecular docking with AutoDock confirmed strong binding affinities between PPDs/PPDQs and core targets. These results suggest that PPDs and PPDQs may promote the onset and progression of bowel cancer and intestinal inflammation by modulating cancer cell death, proliferation, and inflammatory signaling pathways. This research provides a theoretical framework for elucidating the molecular mechanisms of PPD- and PPDQ-induced enterotoxicity, offering insights for the prevention of associated diseases.