The human skin is a recurring target of external aggressions, such as UV radiation, leading to exacerbation of the aging process and the occurrence of skin diseases, such as cancer. Hence, preventive measures should be taken to protect it against these aggressions, consequently decreasing the chance of disease development. In the present study, a topical xanthan gum nanogel containing gamma-oryzanol-loaded nanostructured lipid carriers (NLCs) and nanosized UV filters TiO2and methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT) was developed to assess their synergistic potential in having multifunctional skin beneficial properties. The developed NLCs contained the natural-based solid lipids shea butter and beeswax, liquid lipid carrot seed oil, and the potent antioxidant gamma-oryzanol, with an optimum particle size for topical application (<150 nm), good homogeneity (PDI = 0.216), high zeta potential (−34.9 mV), suitable pH value (6), good physical stability, high encapsulation efficiency (90%), and controlled release. The final formulation, a nanogel containing the developed NLCs and the nano UV filters, showed high long-term storage stability and high photoprotection ability (SPF = 34) and resulted in no skin irritation or sensitization (rat model). Hence, the developed formulation showed good skin protection and compatibility, demonstrating promise as a new platform for the future generation of natural-based cosmeceuticals.