The outermost layer of the epidermis, the stratum corneum (SC), ensures protection against harmful xenobiotics, and alterations in its lipidic matrix composition are related to several cutaneous dysfunctions. The skin barrier function is usually attributed to ceramides, but the role of free fatty acids, such as stearic acid, has been increasingly acknowledged. This research work aimed to develop solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) based on stearic acid and glyceryl distearate, in order to explore the potential of these materials as the basis of lipid nanoparticles. Different blends of stearic acid, Precirol® ATO 5, Capryol® 90 and Tween® 80 were probed to prepare SLN and NLC. These lipid nanoparticles were further characterised according to particle size, polydispersity index (PDI), pH, and viscosity. Accelerated and long-term stability tests were also performed for 90 days, as well as in vivo assays to evaluate safety and efficacy. Overall, most nanoparticles showed interesting properties for topical application if they had sizes less than 300 nm, PDI below 0.3, pH compatible with skin and viscosity lower than 5 mPa.s. In long-term stability studies, the SLN_2 and NLC_2 formulations stood out, as they remained stable over time. In vivo biocompatibility tests conducted in human volunteers showed no negative impact of the formulations when applied openly or under occlusion. Efficacy studies with the most stable nanoparticles made of Precirol® ATO 5 showed an increase in skin hydration. The nanoparticles developed in this study have shown potential to be used for cosmetic purposes, and the blend of lipids provided good biocompatibility and moisturising properties.