Co-eradication of cancer stem cells (CSCs) along with cancer cells have emerged as an immediate necessity to combat the rapid progression, therapeutic resistance, and relapse of cancer. Curcumin (CMN) has been well established for anticancer activity against a variety of cancers with an ability to eliminate CSCs. In spite of its extensive therapeutic potential, clinical applicability is impeded due to its highly hydrophobic nature. In this study, we developed CMN-loaded nanostructure hybrid lipid capsules (CMN-nHLCs) of three sizes (25, 75, and 150 nm) with 4% (w/w) loading capacity using our low-temperature (LT) method. Molecular interaction between different ingredients using fourier transform infrared (FTIR) analysis shows self-arrangement of ingredients into CMN-loaded nHLCs without any chemical bonding. CMN-nHLCs show a controlled release of CMN from nHLCs at 37 °C and long-term storage stability at 4 °C. CMN-nHLCs show ∼2.5-fold enhanced anticancer efficacy compared to free CMN in breast cancer cells (non-bCSCs) and breast cancer stem-like cells (bCSCs). CMN-nHLCs are effectively internalized into MCF-7 cells (non-bCSCs and bCSCs) and cause significant reduction in their mammosphere size/number and stemness. nHLCs provide improved physicochemical properties of CMN and superior anticancer efficacy by co-eradiating both non-bCSCs and bCSCs, suggesting a promising candidature of CMN-nHLCs for breast cancer treatment. © 2020 American Chemical Society.