Inverse bicontinuous cubic phase nanoparticles (cubosomes) have attracted significant attention in recent years, owing to their potential use as delivery vehicles for chemically fragile or poorly soluble drugs and nutraceuticals. Herein we have investigated the use of lipid nanoparticles as a delivery vehicle for curcumin, a compound with demonstrated anti-cancer properties. Curcumin is encapsulated within cubosomes comprised of several different lipid formulations, as well as phospholipid-based liposomes. The entrapment efficiency of curcumin within cubosomes was observed to vary depending on both the nanoparticle architecture and the curcumin concentration. Fluorescence spectroscopy analysis revealed that penetration of curcumin into the hydrophobic region of the bilayer was dependent on lipid composition. Curcumin was typically associated with the polar headgroup region at low concentrations, but transferred to the lipid bilayer region at higher concentrations, particularly in phytantriol cubosomes. Each nanoparticle formulation was characterized using small angle X-ray scattering and dynamic light scattering to assess the structural stability subsequent to curcumin encapsulation. The structure of the cubosomes was generally robust to the addition of curcumin, while the liposomes displayed a large increase in particle size and PDI at higher curcumin concentrations. Finally, the cytotoxicity of each formulation was assessed against murine fibroblast (NIH3T3) and murine melanoma (B16F10) cell lines in order to investigate improvements in curcumin bioavailability following encapsulation in cubosomes, as well as assess potential anti-cancer applications. Increased cytotoxicity of the cubosome-loaded curcumin against the murine melanoma cell-line demonstrates the potential of these nanoparticles as delivery vehicles for curcumin and other poorly water-soluble drugs.