Turmeric is a well-known functional food exhibiting multiple biological activities in health and disease. However, low aqueous solubility and poor bioavailability limit its therapeutic potential. Herein, we investigated the utility of nanoemulsions as a carrier to improve the efficacy of turmeric. Compared with turmeric extract (TE), 5% TE-loaded nanoemulsion (TE-NE), which contains 20-fold lower curcumin content than TE, achieved similar inhibition of palmitate-induced lipotoxicity in HepG2 cells. Exposure of HepG2 cells to 5% TE-NE also suppressed the palmitate-induced accumulation of lipid vacuoles and reactive oxygen species comparably with TE, and was accompanied by decreased levels of sterol regulatory element-binding protein (SREBP)-1, peroxisome proliferator-activated receptor-γ2 (PPAR-γ2), cleaved caspase-3, and poly (ADP-ribose) polymerase (PARP). Consistent with these effects in HepG2 cells, oral administration of 5% TE-NE to mice fed a high fat diet (HFD) markedly suppressed lipid accumulation in liver, leading to a significant reduction in body weight and adipose tissue weight, equivalent to the effects observed with TE. Compared with TE, 5% TE-NE also equivalently inhibited the levels of SREBP-1, PPAR-γ2, cleaved caspase-3, and PARP in the liver of mice fed a HFD. Furthermore, TE and 5% TE-NE significantly improved serum lipid profiles in a similar manner. These observations indicate that nanoemulsions can improve the efficacy of turmeric, thereby eliciting more potent biological efficacy against palmitate- and high fat diet (HFD)-induced cellular damage.