Objectives This study aimed to evaluate the effects of a 16-week creative expression intervention program (CrExp) on the event-related potential (ERP) and task reaction time (RT) in older individuals with mild cognitive impairment (MCI). Methods This study is a randomized controlled clinical trial conducted in the Memory Center of Fujian Provincial hospital. Thirty-six MCI patients were randomly distributed into two groups. One group underwent a 16-week creative expression program (CrExp, n = 18) and the other performed as a control group (CG, n = 18) by general social activities. The amplitude and latency of event-related potential (ERP-P300) from the central (Cz), parietal (Pz), frontal (Fz) cortices and task reaction time (RT) were assessed at baseline, post-interventi on, and 24-week follow-up. Results The CrExp group showed greater differences than CG of P300 latency in Cz (F = 4.37, P = 0.015), Pz (F = 2.78, P = 0.009), Fz (F = 6.45, P = 0.031) brain area after 16 weeks of intervention and in Fz (F = 3.23, P = 0.028), Cz (F = 3.79, P = 0.024), and Pz (F = 5.60, P = 0.036) at 24 weeks follow-up. Also, we analyzed the task reaction time between two groups and found that a shorten reaction time at post-intervention (F = 4.47, P = 0.011) and 24 weeks follow-up (F = 3.12, P = 0.007) in the CrExp group. However, there was no difference in P300 amplitude in either brain area between the two groups. Conclusion The electrophysiological results of the creative expression cognitive therapy group were more obvious than those of the general cognitive therapy group, and the latency and task reaction time may be considered as supported parameters in diagnosing the effects during non-drug therapy intervention in clinical practice.