The synthesis of zinc hexa ferrite (ZnFe12O19) nanostructures using fructose as a green capping agent is introduced through simple sol-gel auto-combustion approach. Response surface methodology (RSM) based on Box-Behnken design (BBD) was used for performance improvement of the nanostructures as a new green nanosorbent. Several techniques were applied to characterize structural, spectroscopic, microscopic, morphological and magnetic properties of the nanostructures. Then, the ZnFe12O19 nanosorbent was applied for surfactant-assisted dispersive liquid-liquid microextraction of betaxolol (BTX). Also, the microextraction step was coupled with optimization and modeling studies in order to ultra-traces determination of BTX using high-performance liquid chromatography-ultraviolet detection (HPLC-UV). The limit of quantification and detection of BTX under the optimized experimental conditions, were achieved 0.11 and 0.03 μg L−1, respectively. Moreover, the good validation criteria results proposed the procedure can be applied in the quantification of BTX in real complicated samples.