Fucosylation is one of the most common glycosylation modifications that is closely related to the occurrence, development, and prognosis of cancer. A change in fucosyltransferase correlations with tumor multidrug resistance has been reported. Multidrug resistance of tumor cells is a major factor affecting chemotherapy efficacy, which often leads to a poor therapeutic effect and prognosis. This review focuses on the relationship between fucosyltransferase family members and their catalytic fucosylation modification and tumor multidrug resistance, briefly summarizes the therapeutic effect of fucosylation inhibitors on tumors, and describes fucosylation analogues as fucosylation inhibitors that may be potential drugs to reverse tumor multidrug resistance. This article provides a basis for fucosylation modification as a drug target to reverse and sensitize tumor drug resistance.