The aim was to develop an optimized albendazole (ALB) nanosuspension to improve its solubility and therapeutic activity as an adjuvant localized therapy for treatment of the pinworm infection to enhance oral treatment outcomes using Box–Behnken design. ALB-nanosuspensions were successfully prepared by antisolvent sono-precipitation technique considering amount of Lecithin, PVP and ultrasonication time as independent variables. All the formulations were characterized regarding their particle size and PDI (dependent variables). Nanoparticle size was significantly increased by increasing lecithin and PVP concentrations while sonication time showed no influence. PDI of the nanosuspension was insignificantly decreased with increasing lecithin concentration and probe-sonication time. Optimum formulation was identified and subjected to solid phase characterization and morphological studies. ALB nanosuspension showed 10 folds increase in solubility over pure albendazole powder. Eventually, we studied the anthelmintic activity of ALB nanosuspension compared to free ALB where nanosuspension treated group showed lesser paralysis and death time than free ALB.