Alternatives and replacements for synthetic chemical-based plant protectants are required. In this study biopolymeric microspheres containing arthropod-derived apitoxin are explored as a possible novel environmentally friendly formulation for plant protection. Here we document the optimization process for microencapsulation of apitoxin into a stable formulation, for ready use in agricultural applications. Efficacy trials were carried out on three different beetle species at various developmental stages (Leptinotarsa decemlineata (Say, 1824.), Tenebrio molitor (Linnaeus, 1758.), Sitophilus granarius (Linnaeus, 1758.)). The encapsulated apitoxin has a steady initial and long residual effect, due to the slow release of apitoxin which is one of its main advantages over other conventional control methods. Microspheres loaded with apitoxin have a detrimental effect on insects, of which it is significantly better gastric compared to contact action (due to pH). The results showed that the highest and fastest mortality was obtained when the highest concentrations (0.6%) were applied, chosen to be economically acceptable. These important findings contribute to knowledge on the application and development of encapsulated apitoxin formulations, and their effectiveness, as an alternative eco-friendly control method in agricultural production.