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Alzheimer’s disease (AD) is one of the leading causes of dementia. As the first common neurodegenerative disease, there are no effective drugs that can reverse the progression. The present study is to report the anti-AD effect of cryptotanshinone (CTS), a natural product isolated from <i>Salvia castanea</i>. It is found that it can alleviate AD-like features associated with Aβ_1-42 toxicity in muscle cells as well as neuronal cells of <i>Caenorhabditis elegans</i> (<i>C. elegans</i>). Further studies showed that CTS reduced the level of reactive oxygen species (ROS) in nematodes, up-regulated the expression of <i>sod-3</i>, and enhanced superoxide dismutase activity. Cryptotanshinone reduced the level of Aβ monomers and highly toxic oligomers in <i>C. elegans</i> while inhibiting the abnormal aggregation of polyglutamine protein. In addition, CTS upregulated the expression of <i>hsp-16.2</i> and downregulated the expression of <i>ace-2</i>. These results suggested that CTS could alleviate oxidative stress and reduce the level of abnormally aggregated proteins and has the potential to be developed as an anti-AD drug candidate.