Fresh-cut potatoes (Solanum tuberosum L.) are susceptible to browning and microbial contamination during storage. In this study, the effects of trans-2-hexenal (E2H), ascorbic acid (VC), dimethyl dicarbonate (DMDC), and the combined treatment of E2H, VC, and DMDC on quality deterioration in fresh-cut potatoes were investigated. The response surface methodology (RSM) demonstrated that E2H, VC, and DMDC concentrations of 0.010%, 0.65%, and 240 mg/L, respectively, were the optimum conditions for fresh-cut potato preservation. Further analysis showed that the combined treatment of E2H, VC, and DMDC was the most effective method of reducing quality deterioration in potatoes compared to the control and individual treatments. Furthermore, the combined treatment of E2H, VC, and DMDC could decrease the accumulation of reactive oxygen species (ROS) via improving antioxidant enzyme activities. Meanwhile, energy-metabolism-related enzyme activities and glutamate decarboxylase (GAD) activity were enhanced, while γ-aminobutyric acid transaminase (GABA-T) activity was reduced via the combined treatment of E2H, VC, and DMDC, which contributed to maintaining high energy levels and GABA content in potatoes. These findings suggested that the combined treatment of E2H, VC, and DMDC could protect membrane integrity through enhancing antioxidant capacity, energy levels, and GABA content to maintain quality in fresh-cut potatoes.