Alzheimer's disease is a major neurodegenerative disease with memory impairment. Amyloid precursor protein is sequentially cleaved by β/γ-secretases, and finally releases the amyloid β (Aβ) peptide. Low aggregated form of Aβ (Aβ oligomer) is proposed as a trigger of Alzheimer's disease. Actually, previous studies showed that acute intracerebroventricular (i.c.v.) injection of Aβ oligomer in mice leads to memory impairment, and also weakens θ oscillations in the hippocampus (5~8 Hz) related to learning and memory. In this study, we explored an endogenous peptide to recover the Aβ oligomer-induced dysfunction in vivo. To address this issue, we focused on p3-Alcβ peptide which is released from Alcadeinβ expressed specifically in neurons, because this peptide is also produced by γ-secretase cleavage in the same manner as Aβ. First, we assessed effects of p3-Alcβ on the cognitive dysfunction using novel object recognition test. An i.c.v. injection of Aβ oligomer (1 μM) impaired the memory performance. However, co-injection of p3-Alcβ (10 μM) fully recovered the Aβ oligomer-induced memory impairment. Second, we assessed the neural dysfunction by recording the θ oscillations in the hippocampus of awake mice. An i.c.v. injection of Aβ oligomer (1 μM) decreased the power of θ oscillation. However, co-injection of p3-Alcβ (10 μM) improved the Aβ oligomer-induced attenuation of θ oscillations. We further found that p3-Alcα, another p3-Alc peptide released from Alcadeinα, has no effects on the Aβ oligomer-induced cognitive and neural dysfunction. These results show that endogenous peptide p3-Alcβ improves Aβ oligomer-mediated cognitive and neural dysfunction in mice. We propose that p3-Alcβ is a new therapeutic target for Alzheimer's disease.