Advances in existing drying techniques are essential for upgrading large scale industries. Enzymes are often degraded by drying processes. Spray drying (SD) has detrimental effects on bioactive molecules at high temperatures. Freeze-drying (FD) is a reference technique capable of drying sensible molecules at low temperature. In this paper, electrostatic spray drying (ESD) was utilized for the first time to encapsulate β-gal (β-galactosidase) and compared with conventional SD and FD techniques. Matrices such as maltodextrin, trehalose, shellac, skim milk and arabic gum were used to encapsulate β-gal. The residual enzyme activity was analyzed based on lactose hydrolysis and quantified using HPLC. Morphologies, particle sizes, shapes and reconstitution times were also compared. SD at inlet air temperature of 170 °C, degraded enzyme functionality and reconstitution ability. ESD at intermediate temperatures (inlet/outlet – 90 °C/44 °C) produced microparticles with better characteristics than SD. In addition, ESD microparticles showed maximum preservation of β-gal in maltodextrin, trehalose, and shellac with a 1–3 kV voltage supply, and the residual enzyme activity was similar to that of FD. Thus, ESD is an alternative technique to FD, which is often considered efficient, but time consuming and expensive. Display omitted •β-galactosidase was efficiently microencapsulated in different stabilizing matrices.•Enzyme activity was highly recovered after ESD & FD microparticles rehydration.•SD with 170 °C inlet air temperature degraded the enzyme functionality.•ESD was capable to encapsulate β-gal with better microparticle characteristics.