Background: Standard treatment of epileptic seizures involves the use of antiepileptic drugs (AEDs). Both AEDs themselves and treatment duration may influence the levels of biochemical parameters, e.g., lipids or homocysteine (HCys), that may increase the risk of cardiovascular diseases. The aim of the present study was to compare the levels of lipid parameters, as well as the concentrations of selected aminothiols (i.e., HCys, cysteine, and glutathione) between epileptic children treated with multiple AEDs and children without epilepsy. Methods: In the study, 21 children with epilepsy treated with two or more AEDs for at least 6 months (8 girls and 13 boys, mean age 7.03 ± 4.51) and 23 children without epilepsy (7 girls and 16 boys, mean age 7.54 ± 3.90) were prospectively analyzed. Lipid parameters, i.e., total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL) and high density lipoprotein (HDL), and levels of selected aminothiols were determined in the blood serum. Results: No differences in the mean levels of lipid parameters and in the mean values of lipid ratios (TC/HDL, TG/HDL, LDL/HDL) were observed between the total groups as well as in the sex subgroups. HCys and cysteine levels did not differ between the patients and controls. We observed significantly lower levels of glutathione in children with epilepsy than in children without epilepsy (1.49 ± 0.35 µmol/L vs. 2.39 ± 1.17 µmol/L, respectively) (p < 0.001). Glutathione level was also lower in boys with epilepsy than in boys without epilepsy (p = 0.007). Similarly, epileptic girls had statistically decreased levels of glutathione when compared to girls without epilepsy (p = 0.006). Conclusions: A lower level of glutathione is observed in pediatric patients with epilepsy treated with two or more AEDs for at least 6 months. This indicates the oxidative stress of the patients treated with AEDs, which in turn may affect their well-being, and in the case of chronic occurrence resulting from long-term treatment, also on the function of the liver and the condition of the cardiovascular system.