The essential oils (EOs) of the aerial parts of Lippia origanoides (LiOr), collected in different localities of the Amazon region, were obtained by hydrodistillation and analyzed by GC and CG-MS. Principle component analysis (PCA) based on chemical composition grouped the oils in four chemotypes rich in mono- and sesquiterpenoids. Group I was characterized by 1,8-cineole and α-terpineol (LiOr-1 and LiOr-4) and group II by thymol (LiOr-2). The oil LiOr-3 showed β-caryophyllene, α-phellandrene and β-phellandrene as predominant and LiOr-5 was rich in (E)-nerolidol and β-caryophyllene. All samples were evaluated for antioxidant activity and inhibition of tyrosinase in vitro and in silico. The highest antioxidant activity by the DPPH free radical method was observed in LiOr-2 and LiOr-5 oils (132.1 and 82.7 mg TE∙mL-1, respectively). The tyrosinase inhibition potential was performed using L-tyrosine and L-DOPA as substrates and all samples were more effective in the first step of oxidation. The inhibition by samples LiOr-2 and LiOr-4 were 84.7% and 62.6%, respectively. The samples LiOr-1, LiOr-4 and LiOr-5 displayed an interaction with copper (II) ion with bathochromic shift around 15 nm. In order to elucidate the mechanism of inhibition of the main compounds, a molecular docking study was carried out. All compounds displayed an interaction between an oxygen and Cu or histidine residues with distances less than 4 Å. The best docking energies were observed with thymol and (E)-nerolidol (-79.8 kcal.mol-1), which suggested H-bonding interactions with Met281 and His263 (thymol) and His259, His263 ((E)-nerolidol).