Recent studies have indicated that polysaccharides, the main component of the Lycium barbarum L. fruit, have beneficial effects (e.g., anxiolytic, antioxidant, and neuroprotective) on humans and rodents. However, the effects of different dosages of such polysaccharides on ovariectomized rats and their underlying mechanisms in the brain have not been evaluated in the literature. Here, we aimed to evaluate the effects of the high and low doses of polysaccharides obtained from Lycium barbarum fruits (HD-LBP and LD-LBP, respectively) on anxious behaviors via behavioral (using the OFT and EPM), biochemical (using ELISA), and immunohistochemical (using immunohistochemical staining) measures in detail. Two weeks after ovariectomy, the rats were randomly assigned to either the treatment conditions [control (DW, 3 mL/kg, p.o., per day), LD-LBP (20 mg/kg, 3 mL/kg, p.o., per day), HD-LBP (200 mg/kg, 3 mL/kg, p.o., per day), 17 β-ES (1 mg/kg, 3 mL/kg, p.o., per day), DZ(1 mg/kg, 3 mL/kg, p.o., per day)] or operation type [SHAM (pseudo-ovariectomized) and OVX (ovariectomized)]. The treatments were applied for 30 consecutive days, and then serum and brain tissue samples of all rats were collected. Biochemical (SOD, CAT, GPX, MDA, and 17 β-ES) and immunohistochemical (BDNF, SER, and apoptosis) analyses of the samples were performed as well. The rats administered HD-LBP and LD-LBP were less anxious than the control groups. The HD-LBP-treated rats had high levels of SOD and low levels of MDA in their serum samples. Moreover, HD-LBP and drug-treated groups had a high number of SER receptors and BDNF-positive cells and a low number of TUNEL-positive cells in their hippocampal brain tissues. The HD-LBP treatments decrease anxious behavior by increasing antioxidant enzyme activities, hippocampal SER and BDNF neurotransmitter levels and decreasing the TUNEL-positive cell count of ovariectomized rats. Given these findings, we suggest that menopause-induced symptoms of anxiety can be reduced by polysaccharides obtained from goji berry fruits, and that these findings will be beneficial for the production studies of natural herbal-origin antianxiety (anxiolytic) drugs in the future. Copyright © 2020 The Author(s).