Brain tumors (BTs) represent a varied group of intracranial neoplasms. Among the treatment methods, radiotherapy is common. However, both the tumor and radiotherapy may induce oxidative stress, potentially impacting tumor progression and eliciting inflammation. This preliminary study aimed to assess the levels of C-reactive protein (CRP), melatonin, malondialdehyde (MDA), and protein carbonyl groups (PCO) in BT patients, both immediately before radiotherapy and 6-8 months after treatment. The study encompassed 16 patients (9 males and 7 females; average age of 51.75 ± 3.07 years) diagnosed with primary BT. Blood samples were procured at two timepoints: initially during the radiotherapy planning phase and, subsequently, after an average of 219.11 ± 14.40 days from the first collection. Blood serum samples underwent biochemical testing. A p-value of less than 0.05 was considered statistically significant. Results, expressed as mean value ± standard error of the mean (SEM), demonstrated a decrease in CRP levels from 11.01 ± 1.02 mg/L to 5.40 ± 0.54 mg/L. Melatonin levels remained comparable at 38.81 ± 2.40 pg/mL and 40.31 ± 2.29 pg/mL, respectively. MDA concentrations reduced from 483.86 ± 8.61 ng/mL to 454.25 ± 9.42 ng/mL, and PCO levels decreased from 200.33 ± 22.76 U/mL to 145.75 ± 6.20 U/mL. Statistically significant variations were noted in the levels of CRP, MDA, and PCO pre- and post-radiotherapy. Among long-term effects of BTs radiotherapy, a decrease of oxidative stress and inflammatory markers could be noticed. Those changes might be important for the patient's health improvement.