The prevalence of psychiatric disorders which are characterized by cognitive decline is increasing at an alarming rate and account for a significant proportion of the global disease burden. Evidences from human and animal studies indicate that neurocognitive development is influenced by various environmental factors including nutrition. It has been established that nutrition affects the brain throughout life. However, the mechanisms through which nutrition modulates mental health are still not well understood. It has been suggested that the deficiencies of both vitamin B12 and omega-3 fatty acids can have adverse effects on cognition and synaptic plasticity. Studies indicate a need for supplementation of vitamin B12 and omega-3 fatty acids to reduce the risk of cognitive decline, although the results of intervention trials using these nutrients in isolation are inconclusive. In the present article, we provide an overview of vitamin B12 and omega-3 fatty acids, the possible mechanisms and the evidences through which vitamin B12 and omega-3 fatty acids modulate mental health and cognition. Understanding the role of vitamin B12 and omega-3 fatty acids on brain functioning may provide important clues to prevent early cognitive deficits and later neurobehavioral disorders.