Objective: To compare the efficacy and safety of levetiracetam and sodium valproate sustained-release tablets in the treatment of adult epilepsy and the influence on bone mineral density and bone metabolism level of patients. Methods: A total of 82 adult patients with epilepsy who were admitted to the hospital from January 2024 to January 2025 were included. According to the treatment methods, they were divided into 40 cases in single group (sodium valproate sustained-release tablets) and 42 cases in combined group (levetiracetam and sodium valproate sustained-release tablets). The clinical efficacy, bone mineral density, bone metabolism and incidence rates of adverse reactions were compared between the two groups of patients. Results: After 3 months of treatment, the total effective rate of treatment in combined group was higher compared to single group (P<0.05). The bone mineral density values of lumbar 2-4 vertebrae, Ward triangle and greater trochanter of femur in the two groups after 3 months of treatment were reduced compared with those before treatment, but the bone mineral density values in combined group were higher than those in single group (P<0.05). After 3 months of treatment, the alkaline phosphatase level in both groups was higher than that before treatment, and the level in combined group was higher (P<0.05). The blood calcium and phosphorus in the two groups were close to those before treatment (P>0.05), and the blood calcium and phosphorus after 3 months of treatment were close between the two groups (P>0.05). The incidence rates of adverse reactions were similar between the two groups (P>0.05). Conclusion: The combination of levetiracetam and sodium valproate sustained-release tablets can enhance the clinical efficacy on adult epilepsy, and it has small influence on bone mineral density, and can enhance the bone metabolism, and it does not increase the occurrence of adverse reactions.