Aporosa octandra (Buch.-Ham. ex D.Don) Vickery is a native species of India. Different parts of the plant are used for the medicinal purpose by the tribal peoples of south-eastern part of India. However, the biological properties of A. octandra have not been studied well. The extracts obtained from the bark of A. octandra were evaluated to determine their protective effect on cognitive impairment and oxidative stress in mice induced by D-galactose using the standard protocol. Different dosages of extract AOE-4 (100, 200, and 300 mg/kg, p.o.) were administered to mice, which were previously treated for six weeks with D-galactose (100 mg/kg s.c.). The D-galactose-induced mice showed significantly impaired cognitive behavior, i.e., oxidative defense, compared to the sham group. Six weeks of treatment with A. octandra extract AOE-4 (100, 200 and 300 mg/kg, p.o.) considerably improved the cognitive behavior and oxidative impairment of mice compared to the control alone (D-galactose). For the phytochemical investigation, the bark of A. octandra was successively extracted with dichloromethane and methanol. The chemical constituents of A. octandra were isolated by multiple column chromatography and characterized by different spectral analyses. (R)-Coclaurine (AO-5), an alkaloid, was isolated along with two other compounds from the AOE-4 extract; three more compounds were also isolated from the AOE-1 extract of the bark of A. octandra. All the compounds were isolated for the first time from the bark of A. octandra, and their structures were established by detailed spectral studies. The structure of compound AO-5 was also investigated and confirmed by X-ray diffraction and DFT studies. This study highlights the protective effect of A. octandra bark extract against D-galactose-induced biochemically dysfunction in mice. (R)-Coclaurine (AO-5) was isolated as one of the major components of A. octandra bark from AOE-4 extract; this compound could be further evaluated for the development of new potential drug candidates.