A combination of two methods, polyelectrolyte self-assembly of fucoidan–chitosan and isocyanide-based multicomponent reactions, was used to obtain submicron polymer particles suitable for lyophilization. Piperine, an alkaloid and the major bioactive compound found in black pepper, is endowed with numerous biological activities; however, its application is hindered by low solubility and poor delivery. To overcome this problem, piperine was loaded into the submicron polymer particles obtained. These particles were subjected to lyophilization to assess their ability to redisperse in aqueous solution after drying and their stability. The characterization of the nanoparticles by dynamic light scattering revealed particle sizes of 219.67 ± 0.61 and 355.63 ± 14.49 nm for fucoidan–chitosan nanoparticles and piperine-loaded nanoparticles, respectively. Also, an irregular spherical piperine-loaded nanoparticle was found using atomic force microscopy. An encapsulation efficiency of 92.78% ± 0.02% was measured with UV/visible spectroscopy. In vitro, the release profile of piperine from the nanoparticles showed a significant release and faster dissolution rate than free piperine. For the release mechanism of piperine from the nanoparticle, the Korsmeyer–Peppas model was the best fit with a correlation coefficient (R2) close to 1. The antioxidant activity of the piperine-loaded nanoparticles was significantly higher than that of the unformulated piperine. The piperine-loaded nanoparticles also exhibited positive stability against stress from lyophilization. Therefore, fucoidan–chitosan nanoparticles to improve the bioavailability of piperine, as well as enhance antioxidant activity, and could be used as a nutraceutical.