Turmeric Essential Oil (TEO) has an antioxidant and anti-inflammatory activity to be formulated in a topical dosage form. Nanoemulgels (Negs) development, based on varying concentrations of emulsifiers and gel formers, affects their characteristics and stability. This study focuses on optimizing TEO-loaded Negs based on physical and mechanical characterization, which have promising topical applications. Negs were created using the high-energy approach and optimized using Response Surface Methodology (RSM) and the Central-Composite Design (CCD) for the optimization of span-80/tween-80 (X1) and Carbopol ® 980. (X2). Observed variable responses were particle size (PS) (Y1), polydispersity index (PDI) (Y2), zeta potential (ZP) (Y3), pH (Y4), spreadability (Y5), and adhesion time (AT) (Y6). Actual responses of Negs were compared with the CCD-RSM predictions to validate the model. In addition, other physical evaluations were observed, such as organoleptic observations, homogeneity, freeze-thaw tests, viscosity, and flow properties. Optimized TEO-loaded Negs were made with 8.68% span-80/tween-80 and 1.18% Carbopol ® 980. The evaluation results showed the optimal TEO-loaded Negs on nano-metric size (182.3 ± 5.5 nm) with low PDI (0.242 ± 0.003), good ZP (-57.23 ± 2.91 mV), pH (4.51 ± 0.02), spreadability (6.0 ± 0.2 cm), and AT (6.45 ± 0.19 s). TEO-loaded Negs have an excellent appearance and did not run phase separation at extreme temperature storage with pseudoplastic thixotropy flow. Thus, the developed TEO-loaded Negs can be a potential delivery system and a promising suitable approach for topical preparations.