The production of palm oil-based submicron emulsions in the presence of Tween 80 has been studied in a liquid whistle hydrodynamic cavitation reactor (LWHCR). Preliminary investigations have been carried out using two orifice plates with the hole diameters of 0.0010 and 0.0016 cm with an aim of investigating the efficiency of LWHCR in the oxidation of aqueous solution of potassium iodide (KI). Based on the preliminary studies, the orifice plate with the smallest hole diameter was chosen for the generation of submicron emulsions. The effect of operating parameters of LWHCR such as the distance between the orifice plate and blade (0.5, 0.6, and 0.8 cm) and the inlet operating pressures (400, 600, and 800 psi) has been successfully investigated and optimized. It has been observed that the minimum droplet size of 476 nm with a PDI of 0.5 was achieved using an orifice plate blade distance of 0.6 cm and at an inlet operating pressure of 800 psi. Furthermore, the influence of the addition of a co-surfactant, Span 80, has also been investigated, and it has been observed that this co-surfactant did not have any impact on the final droplet size attained. Besides, the encapsulation efficiency of curcumin was found to be 88% using the optimum operating conditions of submicron emulsion generation. The stability studies show that the final droplet size for curcumin-loaded submicron emulsions was found to be 532 nm. The present work proved that LWHCR is an efficient yet feasible tool for the generation of submicron emulsion encapsulating curcumin as an active ingredient.