The attention-deficit hyperactivity disorder (ADHD) has a complex etiology, involving the interaction between biological, genetic, and environmental factors. The ADHD pathophysiology remains unknown even though there are hypotheses that inflammatory, hormonal, oxidative and neurotrophic factors are associated. This clinical trial aims to evaluate the contribution of brain derived neurotrophic factor (BDNF), inflammatory and oxidative levels before and after 12 and 24 weeks of methylphenidate use. Methods Patients will be screened upon their entry into Child and Adolescent Psychiatry Teaching Outpatient Clinic of the Medical Course at the Federal University of Viçosa in Minas Gerais, Brazil. One hundred and fifty ADHD treatment-naïve children of both sexes, between 6–14 years old, will be invited to participate, after the ADHD diagnosis by an experienced psychiatrist and the child fulfilling the inclusion criteria. Children and their caregivers will answer questionnaires regarding mental health and the children will undergo neuropsychological tests, physical, nutritional and activity assessment, in addition to blood sampling at baseline, 12 and 24 weeks of methylphenidate use respectively. Discussion This clinical trial intends to verify how the pharmacological treatment changes the plasma BDNF, inflammatory and oxidative levels in treatment-naïve Brazilian children diagnosed for ADHD. Trial Registration Submitted for registration on Brazilian Registry of Clinical Trials (ReBEC). Trial identifier: 13612 Registry name: Níveis de neurotrofina, perfil inflamatório e oxidativo em crianças com TDAH tratadas com metilfenidato.