The pathogenesis of Alzheimer’s disease (AD) is complex as various mechanisms interact with each other and, therefore, intervention from a single target is often ineffective. Many studies have shown that herbal medicines, such as curcumin, fisetin, icariin, and ginsenosides, have significant intervention effects on AD with different treatment mechanisms. Therefore, we have designed this study to know whether the combination of these herbal medicines can have an intervention effect on AD through multiple targets. Amyloid precursor protein/presenilin 1(APP/PS1) double transgenic AD mice were used to study the protective effects of a combination of curcumin, piperine, icariin, and ginsenosides, as well as a combination of fisetin, piperine, icariin, and ginsenosides, which were separately mixed into the feed. These herbal medicinal compounds (HMCs) lowered the serum lipid levels, reduced the Aβ oligomers, decreased the pS404-tau protein, as well as neurofibrillary tangles, and restored the reduction of synaptic protein levels and neuronal death of AD mice without causing toxicity to liver and kidneys. In this study, we found that HMCs have significant intervention against AD through multiple targets, providing a novel therapeutic idea for the prevention of AD.