Loganin significantly upregulated postsynaptic density-95 (PSD95), synaptophysin (SYP), Mfn2, and OPA1 protein levels in the hippocampus of 3×Tg-alzheimer disease (AD) mice, downregulated Drp1, Fis1, LC3II, p62, PINK1, Parkin, TOMM20, and COX isoform IV expression, improved amyloid β-protein (Aβ) deposition and synaptic ultrastructure in 3×Tg-AD mice, restored mitochondrial fission/fusion homeostasis, alleviated the abnormal degradation of mitophagy, and restored the learning and memory ability of 3×Tg-AD mice. Here, SYP is linked to early-onset autosomal dominant Alzheimer disease.