Dysfunction of cholinergic system plays an important role in disease associated with cognitive blockage, such as Alzheimer’s disease (AD). Central administration of scopolamine, an antagonist of acetylcholine receptor, could induce memory impairment in mice. Endocannabinoid system was also implicated in AD, as two peptides agonists of cannabinoid 1 receptor (CB1R), (m)RVD-hemopressin (α) (RVD) and (m)VD-hemopressin (α) (VD) have been reported to inhibit the AD-relating impairment in animal and cell models. More than one-third of the cholinergic cells expressed CB1R, so we speculated that RVD and VD might have ability to inhibit the memory-impairing effect of scopolamine. Our results showed RVD and VD ameliorated the memory toxicity of scopolamine, and the effects of the two peptides could be blocked by CB1R antagonists hemopressin (Hp) and AM251 in novel object and object location recognition tasks in mice. This study suggested that RVD and VD might be potential compounds for the treatment of the disease associated with impairment of cholinergic system.Copyright © 2020. Published by Elsevier Inc.