Physical exercise is recognized as a potential strategy to mitigate the cognitive decline associated with mild cognitive impairment (MCI). This systematic review aims to examine the specific effects of physical exercise on cortical brain activity in patients with MCI, an area that has not been thoroughly explored. We conducted a search across 9 electronic databases for randomized controlled trials assessing the impact of physical exercise on the cortical activity of patients with MCI. The search covered the period from database inception to September 2023. Literature screening, data extraction, and quality assessments were carried out by 2 independent researchers. Meta-analyses were conducted using RevMan 5.3, and publication bias was evaluated using STATA 17.0. This study primarily assessed P300 latency and amplitude, alongside cognitive evaluations using the mini-mental state examination and Montreal Cognitive Assessment. Six high-quality randomized controlled trials, involving a total of 360 participants, were included. Compared to the control group, significant enhancements were observed in the amplitude of central midline electrode (mean difference [MD] = 1.64 [95% confidence interval [CI], 0.92-2.36]; P < .00001), frontal midline electrode (MD = 2.70 [95% CI, 2.02-3.38]; P < .00001), and parietal midline electrode (MD = 2.42 [95% CI, 0.44-4.41]; P = .02). Latency periods of the central midline electrode (MD = -32.40 [95% CI, -40.27 to -24.54]; P < .00001), frontal midline electrode (MD = -12.57 [95% CI, -30.83 to 5.69]; P = .18), and parietal midline electrode (MD = -12.57 [95% CI, -30.83 to 5.69]; P = .81) were also notably influenced. Moreover, overarching cognitive functions as measured by mini-mental state examination (MD = 1.02 [95% CI, 0.61-1.43]; P < .00001) and Montreal Cognitive Assessment (MD = 1.39 [95% CI, 0.67-2.12]; P = .0002) exhibited marked improvement. This meta-analysis suggests that physical exercise can augment the P300 amplitude, reduce the P300 latency period, and, overall, enhance cognitive functionality in individuals with MCI.