BACKGROUND: Acrylamide (AA) is a toxic substance formed when cooking starch-based foods at high temperatures. Studies have shown that AA can cause neurotoxicity, reproductive toxicity and so on. However, there remains limited understanding of the potential skeletal toxicity of AA. OBJECTIVE: The aim of this study was to investigate the potential skeletal toxicity of AA, as well as the potential bone protective effects of Resveratrol (RVT). METHODS: Based on the daily intake of adult women, adult female mice was treated with AA at 0, 0.01, 0.1, 1 mg/kg/d or AA/RVT (1 mg/kg/d AA +10 mg/kg/d RVT) for 8 weeks, and skeletal toxicity were evaluated by RT-qPCR and histopathological techniques. RESULTS: The results found that exposure to AA (0.1 or 1 mg/kg/d) after 8 weeks, osteogenesis exhibited pathological damage characteristics such as inhibition of growth plate function, and reduction of fibrous tissue, and cartilage exhibited pathological damage characteristics such as irregular cell morphology and arrangement, and damage to the tidal line. The results of cellular functional gene testing showed a decrease in the expression of functional genes in osteoblasts and chondrocytes. Meanwhile, after further co-treatment with AA (1 mg/kg/d) and resveratrol (RVT) (10 mg/kg/d), we found that RVT restored AA-induced damage to osteogenesis and cartilage, and reduced the high apoptosis and oxidative stress levels in osteogenesis/cartilage after AA exposure. CONCLUSION: In summary, this study confirmed the skeletal toxicity of AA on female adult mice, and further clarified the antioxidant protective effect of RVT on this toxicity.