To increase the oral bioavailability of curcumin and genistein, we fabricated nanostructured lipid carriers (NLCs), and the impact of these carriers on bioaccessibility of curcumin and genistein was studied. Entrapment efficiency was more than 75% for curcumin and/or genistein-loaded NLCs. Solubility of curcumin and/or genistein in simulated intestinal medium (SIM) was >75% after encapsulating within NLCs which otherwise was <20%. Both curcumin and genistein have shown good stability (≥85%) in SIM and simulated gastric medium (SGM) up to 6 h. Coloading of curcumin and genistein had no adverse effect on solubility and stability of each molecule. Instead, coloading increased loading efficiency and the cell growth inhibition in prostate cancer cells. Collectively, these results have shown that coloaded lipid based carriers are promising vehicles for oral delivery of poorly bioaccessible molecules like curcumin and genistein.