Thermal treatment and composting are effective methods of degrading antibiotics and organic matter in penicillin fermentation residues (PFR), respectively. However, the composting efficiency and environmental safety of thermally treated PFR (HT-PFR) remain unclear. In this study, HT-PFR was composted with cattle manure and maize straw at ratios of 0:1:1 (CK), 1.5:1:1 (T1), and 5:1:1 (T2). Changes in physicochemical properties, seed germination index (GI), and microbial antibiotic resistance genes (ARGs) were determined. Addition of HT-PFR significantly reduced the C:N ratio of each compost (P