Cancer is a serious healthy issue worldwide and cause death to human. Drug resistance is a key factor for the successful treatment of various types of cancers. Phytochemicals have many pharmacological activities with low side effects. Several phytochemicals have been tested in clinical trials as chemosensitizers or anticancer drugs with low side effects. The molecular mechanism of anticancer and reversing multidrug resistance of phytochemicals by modulating signaling transduction or target gene expression are discussed in this article. In this study, we will review the pharmacological activities of natural compounds from herb with anticancer activities and multidrug resistance modulators including berberine, capsaicin, curcumin, 6-gingerol and piperine.