Honokiol, a plant bioactive compound, is derived from the Magnolia genus and has several pharmacological advantages including anti-inflammatory, antiviral, neuromodulatory and anti-tumour activities. However, honokiol’s pharmaceutical utility is constrained by its poor solubility in water. Nanotechnology has been widely used to address this issue to make anticancer medications more effective by increasing their water solubility. Furthermore, the stability of the nanoparticles is one of the most important factors affecting the safety and efficacy of the drug. In this study, honokiol-loaded PLGA − PEG nanoparticles were synthesised and the stability of this nanosystem was evaluated in two conditions that are normal condition and accelerated-aging condition. The parameters used to evaluate the stability of the nanocarrier system include particle size, polydispersity index, zeta potential, morphology, encapsulation efficiency, and loading capacity. All of the samples were stored at three temperatures of 4 °C, 27 °C and 40 °C, and assessed at four times of 0 month, 1 month, 2 months, and 3 months. The physicochemical parameters of nanoparticles after three months of storage showed greater stability at 4 °C compared to 27 °C and 40 °C. There were no significant differences in the parameters of samples stored in three months at 4 °C, meanwhile, the parameters of those stored at 27 °C and 40 °C fluctuated considerably. Therefore, the results show that storing samples at 4 °C allows maintaining the stability of the nanosystem for a long time.