This study is aimed to identify the effects of atmospheric and low-pressure plasma on milk individually and in combination, as the plasma generated and applied at different conditions have variations in the effect on food. Plasma bubbling unit (200 V and 0.24 A) was used for atmospheric plasma and Dielectric Barrier Discharge discharge plasma (70 Pa) with milk passing between the electrodes was used for low-pressure plasma. After treatment, the initial coliform load of 7.62 log CFU/ml was decreased by a maximum of 1.26, 1.58, and 2.2 log reduction, when milk was treated using low-pressure plasma (2 kV and 3 ml/min milk flow rate), plasma bubbling (10 min) and combination of both atmospheric bubbling and low-pressure plasma application (10 min bubbling +2 kV and 3 ml/min milk flow rate) respectively. The conductivity (significantly increased) and pH (slight reduction) of milk supported the presence of reactive species. However, alkaline phosphatase activity was not eliminated in plasma-treated milk; the initial activity in terms of mg phenols/ml of milk was 23.20 which was reduced to 22.57 in low-pressure plasma and 22.35 in plasma bubbling, however, it increased while both the treatments were combined. The sodium dodecyl sulfate–polyacrylamide gel electrophoresis analysis uncovered that the plasma processing didn’t have any prominent impact on the protein fractions in milk. Though plasma bubbling was effective compared to low-pressure plasma, the combination was proved to have a synergistic effect on milk. However, the enzyme structure needs to be studied in the future for analyzing the exact change in the activity.