The antioxidant effects of individual natural compounds have been extensively investigated. However, studies on their interactions are still lacking. This study aimed to observe the interaction effect of ginger extract (GE) combined with ascorbic acid on antioxidant activity by applying response surface methodology. The results from the quadratic model showed that individually tested DPPH free radical scavenging capacities of GE and ascorbic acid manifested positive effects on the antioxidant index (AI%). However, interaction of their combination demonstrated an antagonistic effect that negatively influenced the AI%. An optimization process revealed that the highest AI% could be achieved by applying maximum effective concentrations of GE (0.49 mg/mL) and ascorbic acid (0.82 mg/mL). Although, the mechanisms behind these interactions need to be further explored, the results of this study suggested that antagonistic interaction between the combination of ginger or other herbal extracts with ascorbic acid should be taken into consideration to prevent any potential health complications.