This study aimed to improve the pharmacokinetic behavior of polyunsaturated fatty acids (PUFAs) oxidation to enhance oxidative stability for inhibiting formation of toxic hydroperoxides, develops off-flavors and shortens shelf-life. Nanostructured lipid carrier (NLC) co-encapsulating omega-3 fish oil and α-tocopherol was successfully prepared by melt blending and hot sonication method to enhance the oxidative stability of the fish oil. Encapsulation efficiency (EE) and in vitro release, the oxidative stability of prepared nanoparticles (NPs) were measured using detection of peroxide value (PV) and thiobarbituric acid (TBA) during 40 days. Electron microscopy and particle size analysis showed dispersed and homogenous NPs with an average diameter of 119 nm. Sustained oil release at a physiologic pH, and longterm stability in terms of the size, zeta, and dispersity of NPs was achieved after 75 days of storage. The omega-3 fish oil co-encapsulated with α-tocopherol in the NLC possessed better oxidative stability compared with the all other formulations. Also, it was found that the NLC as an encapsulation method was more successful to inhibit the formation of the primary oxidation products than the secondary oxidation products. Generally, these findings indicated that co-encapsulation of fish oil and α-tocopherol within the NLC can be a suitable delivery system in order to enrich foodstuffs, in particular clear beverages.