Natural plant extracts are widely recognized for their bioactive potential, yet their use is often hindered by poor physicochemical stability and limited oral absorption. Peronema canescens Jack. (Sungkai) leaves have traditionally been employed for their immunostimulatory and antioxidant effects, but their application in pharmaceutical formulations is restricted due to low solubility in water and instability in conventional preparations. This study focused on the development of a nanoemulsion-based delivery system for the ethanol extract of Peronema canescens (P. canescens) leaves and evaluated its antioxidant and immunomodulatory properties. The nanoemulsions were formulated as oil-in-water systems and characterized for droplet size, uniformity, optical clarity, and physical stability. Antioxidant potential was measured using the DPPH radical scavenging assay, expressed as IC₅₀, while immunomodulatory effects were assessed in vivo through hematological parameters after oral administration. The SNEDDS formulations exhibited nanoscale droplets (40–59 nm), high transparency (82–98% transmittance), and stable physical properties. Extract-loaded formulations generally displayed strong antioxidant activity with IC₅₀ values below 50 ppm, although the crude extract showed slightly superior radical scavenging. In vivo, the formulations containing P. canescens extract influenced total leukocyte counts to varying degrees, whereas unloaded formulations had negligible effects. Some formulations produced leukocyte levels comparable to or exceeding those of the crude extract and positive control, while hemoglobin, erythrocyte, and hematocrit levels remained within normal physiological ranges. These findings demonstrate that nanoemulsion-based systems can preserve the antioxidant activity of P. canescens leaf extract and modulate immune responses effectively in vivo. This approach offers a practical strategy to enhance the stability, consistency, and potential application of plant-derived bioactive compounds in nutraceutical and phytopharmaceutical development.