Microplastics' (MPs) capacity to sorb antibiotics in soil ecosystems poses emerging risks, yet their combined toxic effects on soil fauna remain poorly understood. Consequently, we examined the gut toxicity and antibiotic resistance genes (ARGs) of polystyrene MPs (PS-MPs) and the macrolide antibiotic roxithromycin (ROX) in Eisenia fetida. Overall, although co-exposure suppressed gut barrier gene expression (occludin and ZO-1), it did not worsen bacterial translocation (LPS and LBP) relative to single exposures, which is associated with the significant upregulation of antibacterial defense indicators (TLR and CCF), potentially enhancing bacterial clearance. Additionally, PS-MPs mediated the reduction of ROX bioaccumulation by 34.78%, which contributed to the antagonistic interactions observed across multiple indicators, including attenuated deterministic assembly of gut microbiota and ARGs under co-exposure. Beyond enriching resistant Actinobacteria (e.g., Streptomyces and Actinophytocola), ROX also enriched plastisphere-associated pathogenic taxa Escherichia and Enterococcus, as did PS-MPs. These taxa were closely implicated in gut barrier dysfunction and exhibited the strongest correlations with gut ARGs and mobile genetic elements (MGEs) profiles, particularly macrolide-lincosamide-streptogramin B (MLSB) resistance genes (mphA-01, oleC) and MGEs (intI-1(clinic), tnpA-02). Though co-exposure did not increase gut ARGs and MGEs abundance, the enrichment of gut-dominant MLSB resistance genes and MGEs extended to earthworm body tissue, notably driven by PS-MPs, while ROX increased intI-1 (clinic), the strongest contributor to overall variation. PLS-PM revealed that tissue ARGs and MGEs enrichment was associated with gut bacterial translocation driven by dysbiosis-induced activation of LPS-TLR signaling pathways, raising concerns about ARGs dissemination through earthworm-derived traditional medicine and food chains.