Ionotropic gelation followed by polyelectrolyte complexion was used for the synthesis of nanoparticles based on sodium alginate (NaAL) and chitosan (CS) for encapsulation of ibuprofen (IBP), Fourier transform infrared spectroscopy, differential scanning calorimetry, field-emission scanning electron microscopes, percentage of encapsulation efficiency and loading capacity have been used to confirm the synthesis and encapsulation of IBP. The results obtained show that they have a size of around 100 nm. In vitro drug release and evaluation of anti-inflammatory activity in different media indicate that the nanoparticles are pH-sensitive and permit the protection of the drug against total dissolution in the gastric medium, control its release, and it increases the solubility and biological activity of IBP. The analytical data of the in vitro drug release in the simulated gastric fluid (SGF), simulated interstitial fluid (SIF) and phosphate buffered saline (PBS) were fitted to the different kinetic models (zero-order, first-order, Higuchi, Korsmeyer–Pepass and Kopcha), and the results indicate that IBP is released by diffusion-controlled in SIF and PBS, and by erosion-controlled in the SGF. The toxicity of nanoparticles was tested against Artemia salina that displayed non-toxicity effects. In vitro biodegradation by lysozyme and all the results obtained indicated that a NaAL/CS nanoparticles are a promising system for IBP release that can achieve pseudo-zero-order kinetics.