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Poly(d,l-lactic acid)-glycerol (PDLLA-G)-based nanoparticles (NPs) were fabricated for the intravenous delivery of curcumin (CUR). NPs with a mean diameter of approximately 200 nm, a narrow size distribution, and capable of efficient drug encapsulation were prepared using an emulsification-solvent evaporation method. The stability of NPs was verified in water, phosphate buffered saline (PBS), and serum after 24-h incubation. A sustained drug release pattern was observed, and the amount of CUR released in acidic media (pH 5.5) was higher than in media at physiological pH (pH 7.4). Blank NPs (without drug loading) did not exhibit severe cytotoxicity in MDA-MB-231 human breast adenocarcinoma cells. The in vitro anti-tumor efficacy of CUR-loaded NPs in MDA-MB-231 cells was comparable to that of a solution of CUR. Pharmacokinetic studies in rats showed that the in vivo clearance (CL) of CUR in the NP-treated group was lower than the group treated with CUR solution. Therefore, encapsulation of CUR in PDLLA-G NPs was shown to enable prolonged circulation of the drug in the blood stream and guarantee improved anticancer activity after intravenous injection. These biocompatible NPs could be an efficient nano-sized injectable formulation for CUR delivery.