Introduction: Spermidine, a naturally occurring polyamine found in various foods, has been linked to enhanced autophagy and has shown potential cognitive benefits in previous human studies. This mini-review aimed to evaluate the evidence on spermidine’s effect on the adult population’s cognitive functions. Methods: Randomized clinical trials, controlled cohort/cross-sectional, and controlled before-after studies assessing spermidine consumption/supplementation compared to placebo, non-placebo comparators, or regular diet evaluating cognitive function in adults were included. A comprehensive search in MEDLINE, EMBASE, and CENTRAL yielded 1726 records. After duplicate title/abstract and full-text screening, 17 studies were assessed for eligibility, and three were included in the review. Results: All studies were randomized controlled trials in adults aged 60-96. Doses of spermidine supplementation ranged from 0.9mg to 3.3mg. Wirth 2018 (30 participants) and Pekar 2021 (85 participants) showed an improvement in cognitive performance after three months of spermidine supplementation measured with the Mnemonic Similarity Task (MST) and the CERAD-Plus test, respectively. Schwarz 2022 (100 participants) did not find a significant change in memory performance after 12 months of spermidine supplementation compared to placebo measured with MST. Two studies were at high risk of bias, while one study was judged to have a low risk of bias using the Cochrane risk of-bias tool for randomized trials 2 (RoB 2). Conclusion: Current evidence of the effect of spermidine on cognitive function shows inconsistent results based on a few studies with low spermidine doses and a small number of participants. Further evidence is needed to assess its actual effect.