The skin serves as the primary body barrier against external threats, with facial skin being particularly exposed and clinically significant. Skincare products—such as moisturizers, cleansers, and serums—are designed to protect, nourish, and rejuvenate the skin. This study aimed to extract Syzygium myrtifolium (SM) leaves, synthesize them into nanoparticles, and formulate antioxidant serum sprays. SM leaves were macerated in 70% ethanol (pH 2) and concentrated using a rotary evaporator. The resulting extract was characterized and converted into nanoparticles via a precipitation method. Nanoparticle characterization included particle size (252.7 nm), polydispersity index (0.459), zeta potential (−27.2 mV), and entrapment efficiency (47.91%). Both the extract and nanoparticles were formulated into serum sprays and evaluated for physicochemical properties, antioxidant activity, and in vitro release using a Franz diffusion cell. The serum sprays appeared as a clear to pale yellow liquid with a characteristic odor, uniform consistency, appropriate viscosity and spreadability, rapid drying time (<3 minutes), and an average pH of 7.20. Antioxidant activity, expressed as IC₅₀, was 15.96 ppm (extract), 32.59 ppm (nanoparticles), 32.29 ppm (extract-based serum, EbSS), and 59.98 ppm (nanoparticle-based serum, NbSS). Franz cell analysis showed flux values of 1.72 μg/cm²/min (EbSS) and 1.79 μg/cm²/min (NbSS), with corresponding permeability coefficients of 2.78 cm/min and 2.90 cm/min, and diffusion coefficients of 3.33 cm²/min and 3.48 cm²/min, respectively. Overall, the SM extract was successfully formulated into nanoparticle and serum spray forms, with NbSS exhibiting superior diffusion performance.