Background: Research in sport, military, and aerospace populations has shown that mental fatigue may impair cognitive performance. The effect of nutritional interventions that may mitigate such negative effects has been investigated. This systematic review and meta-analysis aimed to quantify the effects of nutritional interventions on cognitive domains often measured in mental fatigue research. Methods: A systematic search for articles was conducted using key terms relevant to mental fatigue in sport, military, and aerospace populations. Two reviewers screened 11,495 abstracts and 125 full texts. A meta-analysis was conducted whereby effect sizes were calculated using subgroups for nutritional intervention and cognitive domains. Results: Fourteen studies were included in the meta-analysis. The consumption of energy drinks was found to have a small positive effect on reaction time, whilst the use of beta-alanine, carbohydrate, and caffeine had no effect. Carbohydrate and caffeine use had no effect on accuracy. Conclusions: The results of this meta-analysis suggest that consuming energy drinks may improve reaction time. The lack of effect observed for other nutritional interventions is likely due to differences in the type, timing, dosage, and form of administration. More rigorous randomized controlled trials related to the effect of nutrition interventions before, during, and after induced mental fatigue are required.