Glioblastoma multiforme (GBM) is one of the most aggressive brain malignancies, with treatment failure often resulting from the restrictive blood–brain barrier (BBB) and the poor solubility of therapeutic agents. Apocynin, a NADPH oxidase inhibitor with anticancer and neuroprotective potential, suffers from low aqueous solubility, limited permeability, and poor bioavailability. To address these challenges, mucoadhesive chitosan-coated self-nanoemulsifying drug delivery systems (SNEDDS) of apocynin were developed and optimized for intranasal delivery. SNEDDS were prepared using Capryol 90 (oil), Tween 20 (surfactant), and Transcutol HP (co-surfactant) and optimized via a Box–Behnken design. The optimized formulation exhibited a mean droplet size of 112.4 ± 3.2 nm, a polydispersity index of 0.21 ± 0.04, and a zeta potential of –18.7 ± 2.1 mV, confirming nanoscale uniformity and stability. After chitosan coating, the zeta potential shifted to +24.6 ± 1.9 mV, indicating successful surface modification and improved mucoadhesive properties. Both uncoated and chitosan-coated SNEDDS demonstrated more than 90% drug release; however, the chitosan-coated system reduced burst release, providing controlled release and minimizing dose dumping. Dissolution studies showed an approximately 4.5-fold enhancement in release compared with pure apocynin. Stability evaluation under temperature variation and freeze–thaw cycles confirmed formulation robustness. SEM, DSC, and PXRD analyses revealed conversion of apocynin from crystalline to amorphous form, correlating with enhanced solubility and dissolution. Collectively, chitosan-coated SNEDDS present a promising mucoadhesive and controlled intranasal delivery platform for apocynin in glioblastoma therapy.