Folate receptors (FRs) are overexpressed on activated macrophages in inflammatory diseases. In this regard, the FRs-targeting strategy is a good option for the diagnosis and treatment of macrophage-mediated diseases. Here, we developed FRs-targeted nanomaterials that specifically deliver the anti-atherogenic drug lobeglitazone into macrophage foam cells via a strong binding affinity to FRs. The prepared FRs-targetable nanodrug is nontoxic to macrophage foam cells and efficiently delivers lobeglitazone into macrophage foam cells via the FRs-mediated endocytosis. Consequently, the FRs-targetable nanodrug significantly decreases the formation of foam cells by inhibiting the accumulation of lipid droplets in macrophage foam cells.