Extracts made from the leaves of the mango food plant (Mangifera indica L., Anacardiaceae) have a long history of medicinal usage, most likely due to particularly high levels of the polyphenol mangiferin. In rodent models, oral mangiferin protects cognitive function and brain tissue from a number of challenges and modulates cerebro-electrical activity. Recent evidence has confirmed the latter effect in healthy humans following a mangiferin-rich mango leaf extract using quantitative electroencephalography (EEG). The current study therefore investigated the effects of a single dose of mango leaf extract, standardised to contain >60% mangiferin (Zynamite®), on cognitive function and mood. This study adopted a double-blind, placebo-controlled cross-over design in which 70 healthy young adults (18 to 45 years) received 300 mg mango leaf extract and a matched placebo, on separate occasions, separated by at least 7 days. On each occasion, cognitive/mood assessments were undertaken pre-dose and at 30 min, 3 h and 5 h post-dose using the Computerised Mental Performance Assessment System (COMPASS) assessment battery and the Profile of Mood States (POMS). The results showed that a single dose of 300 mg mango leaf extract significantly improved performance accuracy across the tasks in the battery, with domain-specific effects seen in terms of enhanced performance on an ‘Accuracy of Attention’ factor and an ‘Episodic Memory’ factor. Performance was also improved across all three tasks (Rapid Visual Information Processing, Serial 3s and Serial 7s subtraction tasks) that make up the Cognitive Demand Battery sub-section of the assessment. All of these cognitive benefits were seen across the post-dose assessments (30 min, 3 h, 5 h). There were no interpretable treatment related effects on mood. These results provide the first demonstration of cognition enhancement following consumption of mango leaf extract and add to previous research showing that polyphenols and polyphenol rich extracts can improve brain function.