We aimed to investigate the effects of topiramate monotherapy on anthropometric indexes, insulin resistance, and serum leptin and lipid levels in 33 premenopausal women (mean age ± standard deviation: 26.7 ± 7.1 years) with cryptogenic epilepsy. Body mass index (BMI), waist circumference and serum leptin, insulin and lipid levels were measured at baseline and at 6 months after initiation of topiramate. We found reductions in BMI ( p < 0.001), waist circumference ( p < 0.001) and serum high-density lipoprotein (HDL) cholesterol levels ( p = 0.011). We also found significant improvements in insulin resistance ( p = 0.023), but not in serum leptin levels ( p = 0.45). Our results suggest that topiramate treatment in women with epilepsy is associated with reduced BMI and waist circumference and improvement in insulin resistance; however, according to our data, topiramate treatment is also associated with lower HDL cholesterol levels, which may substantially increase vascular disease.