Nanosuspensions as aqueous formulations need to be preserved. However, preservatives could vitiate the physical stability of suspensions and to a greater extent nanosuspensions. The impact of six varied preservatives on the physical stability of previously prepared nanosuspensions was studied. The hesperetin nanosuspensions were stabilized using plantacare 2000.30 cycles of high pressure homogenization (HPH) led to a mean photon correlation spectroscopy (PCS) diameter of 335 nm. The preservatives were, caprylyl glycol, Euxyl PE9010, Hydrolite-5, MultiEx naturotics, Phenonip and Rokonsal PB5. On one hand, aggregations were noticed after adding caprylyl glycol, MultiEx naturotics and Phenonip reaching PCS mean diameters of about 500, 1070, 800 nm, respectively. While on the other hand Euxyl PE9010, Hydrolite-5 and Rokonsal PB5 have not significantly affected the physical stability of the nanosuspensions with mean PCS diameters of about 365, 332, 350 nm, respectively. The obtained nanosuspensions were further characterized by measuring zeta potential. From the obtained data it was found that the lipophilicity of the used preservatives demonstrates major influence on the stability of the nanosuspensions, i.e. the higher lipophilicity of the preservative, the stronger the destabilizing effect. Briefly, highly hydrophilic preservatives are recommended to preserve hesperetin nanosuspensions in order to maintain their physical stability during storage.