Mushrooms contain bioactive compounds with documented antioxidant and anti-inflammatory actions. Here, we present a systematic evaluation of epidemiological and clinical studies that investigate the role of mushrooms, either as a separate or integral dietary component, on neurocognition and mood. Following a search of four databases, a total of 34 human studies examining the effect of different mushrooms across varying age cohorts and health statuses were selected for inclusion. Epidemiological studies included in this review (n = 24) revealed a significant benefit of dietary patterns that included mushrooms of any species on cognition and mood in both healthy and compromised populations. However, the results obtained from intervention studies (n = 10) were mixed. Studies mainly investigated Lion's Mane (Hericium erinaceus), showing some enhancement of mood and cognitive function in middle-aged and older adults. Further acute and chronic human intervention studies are needed, using adequate sample sizes, employing appropriately sensitive neurocognitive tests, and investigating a range of dietary mushrooms, to confirm the effects of mushroom supplementation on neurocognition and mood in humans.