Age-related changes in nutritional status can play an important role in brain functioning. Specific nutrient deficiencies in the elderly may exacerbate pathological processes in the brain. Consequently, the potential of nutritional intervention to prevent or delay cognitive impairment and the development of dementia is an important topic. A randomized, double-blind, placebo-controlled trial has been performed in 25 elderly subjects (86 ± 6 years, 20 females, 5 males) with mild cognitive impairment (MCI). These subjects were randomly assigned to supplement their diet with either an oily emulsion of docosahexaenoic acid (DHA)-phospholipids containing melatonin and tryptophan (11 subjects) or a placebo (14-matched subjects) for 12 weeks. The main aim of this study was to evaluate the efficacy of the dietary supplement on cognition, by the assessment at the start and after 12 weeks of: (1) Orientation and other cognitive functions: Mini-Mental State Examination (MMSE); (2) Short-term memory: digit, verbal, and spatial span (digit span; verbal span; Corsi's test); (3) Long-term memory: Rey's auditory-verbal learning test; 'short story' test; Rey-Osterrieth complex figure (recall); (4) Attentional abilities: attentive matrices; (5) Executive functions: Weigl's sorting test; phonological fluency 'FAS'; (6) Visuo-constructional and visuo-spatial abilities: copy of simple drawings; Rey-Osterrieth complex figure (copy); (7) Language: semantic fluency; (8) Mood: Geriatric Depression Scale (GDS). Moreover, Sniffin' Sticks olfaction test and Mini Nutritional Assessment (MNA) have been performed. After 12 weeks, a significant treatment effect for the MMSE (P < 0.001) and a positive trend for the semantic verbal fluency was found in the supplement group (P < 0.06). A significant treatment effect was found out for the olfactory sensitivity assessment (P < 0.009). As regards the nutrition evaluation, after 12 weeks of treatment the supplemented group showed an improvement in the MNA score with a significant difference relative to placebo (P < 0.005). Older adults with MCI had significant improvements in several measures of cognitive function when supplemented with an oily emulsion of DHA-phospholipids containing melatonin and tryptophan for 12 weeks, compared with the placebo.